The DOI matches its Crossref record; 359 of the 369 references it cites were found in a registry or an index; 9 of the 279 sources its claims cite were checked for support.
Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature
Open accessAbstract
Clinicopathologic correlation studies are critically important for the field of Alzheimer disease (AD) research. Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations. Many sources of data variability can weaken the apparent correlation between cognitive status and AD neuropathologic changes. Indeed, most persons in advanced old age have significant non-AD brain lesions that may alter cognition independently of AD. Worldwide research efforts have evaluated thousands of human subjects to assess the causes of cognitive impairment in the elderly, and these studies have been interpreted in different ways. We review the literature focusing on the correlation of AD neuropathologic changes (i.e. β-amyloid plaques and neurofibrillary tangles) with cognitive impairment. We discuss the various patterns of brain changes that have been observed in elderly individuals to provide a perspective for understanding AD clinicopathologic correlation and conclude that evidence from many independent research centers strongly supports the existence of a specific disease, as defined by the presence of Aβ plaques and neurofibrillary tangles. Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review synthesizes clinicopathologic correlation literature on Alzheimer disease (AD) and concludes that AD neuropathologic changes—Aβ plaques and neurofibrillary tangles—are strongly linked to cognitive impairment, with neocortical neurofibrillary tangle burden correlating best with severity. It argues that Aβ plaques alone are not sufficient for advanced AD dementia and that concomitant non-AD pathologies often weaken apparent correlations.
Key findings
- Evidence from many independent research centers supports AD as a specific disease defined by Aβ plaques and neurofibrillary tangles, but the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.
- Aβ plaques alone do not seem sufficient for advanced clinical AD dementia; neuritic plaques correlate with antemortem cognitive impairment better than diffuse Aβ plaques, and neocortical NFTs correlate more strongly than allocortical or subcortical NFTs.
- In a review of 11 studies comprising 555 subjects without dementia, 12 brains were Braak stage V (2.2%) and 3 were Braak stage VI (0.5%); among thousands of cases, there was no report of a thoroughly documented individual with truly “end-stage” neocortical NFT pathology who lacked antemortem cognitive impairment proximal to death.
- Concomitant pathologies are common and contribute noise: 75% to 90% of patients older than 90 years have some degree of cerebrovascular disease pathology, and hippocampal sclerosis affects up to 20% of individuals in advanced age and correlates with cognitive impairment independently of AD.
Methods
- Design: narrative literature review of clinicopathologic correlation (CPC) studies on AD neuropathologic changes and cognitive status, written from the perspective of neuropathologists and clinicians.
- Data/sample: human autopsy CPC studies, including more than 40 studies assessing Aβ plaques and numerous studies assessing NFTs; highlighted large autopsy series from at least 18 different research centers, with inclusion criteria of more than 40 patients, neuropathologic assessment of both NFTs and AβPs in cerebral neocortex, broad pathologic severity, and nondichotomous correlation with cognitive status.
- Main analysis: qualitative synthesis of study findings, discussion of sources of bias and variability, and comparison of correlations between Aβ plaques, neuritic plaques, NFTs, and antemortem cognitive impairment; no pooled meta-analysis is reported.
Limitations
- The paper states that CPC studies face numerous potential biases: autopsy selection bias, nonrandom clinic- or hospital-based samples, concentration on middle- and upper-income whites in advantaged countries, imperfect and evolving clinical and pathologic assessments, variable time between final clinical evaluation and autopsy, competing mortality risks, and high prevalence of concurrent diseases.
- The paper states that autopsy provides only cross-sectional data and cannot prove molecular mechanisms; pathologic assessments identify deviations from “normal” but do not prove that plaques or tangles are proximate to the ultimate neurotoxic species.
- The text makes evident that this is a narrative review rather than a systematic review or meta-analysis, and its highlighted large-series table uses selective inclusion criteria; the authors also note that not all AD cases fall within the same spatial continuum of NFT distributions and that Braak staging masks variability in lesion density within a given stage.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
92 Not checked yet · 37 Own interpretation · 21 No basis given · 9 Own method · 5 Partly supported · 1 Supported · accuracy not yet measured
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Abundant evidence from many independent studies indicates that Aβ peptides and other plaque substances (in their various molecular forms) may be neurotoxic, both directly and through secondary responses to stress, injury, and inflammation (46, 82, 83).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
- Not checked yetcites [46] source
- Partly supportedcites [82] sourceExperimental — accuracy not yet measured
The Conclusions (page unavailable) report that soluble Aβ oligomers impair synaptic function and structure, supporting the claim that an Aβ form may be harmful. The paper distinguishes these oligomers from monomers and does not establish neurotoxicity for other plaque substances or through secondary responses to stress, injury, or inflammation. (LLM, conf=0.85)
- Partly supportedcites [83] sourceExperimental — accuracy not yet measured
The paper describes direct Aβ toxicity, increased neuronal vulnerability to oxidative and metabolic stress, and inflammatory responses around amyloid plaques (Abstract; no page given). It does not establish that other plaque substances, across their various molecular forms, are themselves neurotoxic, so that broader part of the claim is unsupported by this source. (LLM, conf=0.84)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“The interval between initial ADD clinical diagnosis and death is approximately 8 years (129), but AβPs and NFTs are present well over a decade before death (130-138).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
- Partly supportedcites [130] sourceExperimental — accuracy not yet measured
The Discussion (page not provided) says Alzheimer’s-related neuropathological changes can precede symptoms and reports amyloid accumulation and neurofibrillary tangle changes in young people. It describes the pre-symptomatic interval as being of unknown duration, however, and does not establish that both lesions are present well over a decade before death. (LLM, conf=0.86)
- Not checked yetcites [131] source
- Not checked yetcites [132] source
- Not checked yetcites [133] source
- Not checked yetcites [134] source
- Not checked yetcites [135] source
- Not checked yetcites [136] source
- Partly supportedcites [137] sourceExperimental — accuracy not yet measured
The Discussion (p. 7) reports amyloid-plaque deposits in people with preclinical Alzheimer’s disease, before diagnosis. It does not establish that both AβPs and NFTs are present well over a decade before death; the paper’s timing discussion concerns cognitive impairment before diagnosis, not pathology before death. (LLM, conf=0.83)
- Not checked yetcites [138] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“In autopsy series associated with dementia clinics, a higher proportion of non-AD tauopathies are seen, presumably due to recruitment bias (111).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Tangle-Only” or “Tangle-Predominant” Dementia and Other Non-AD Tauopathies
What the sources say
- Partly supportedcites [111] Schneider, 2009, The neuropathology of older persons with and without dementia from community versus clinic cohorts, J Alzheimers Dis sourceExperimental — accuracy not yet measured
The Results (Probable AD in the community versus clinic; page unavailable) report more atypical diagnoses in the clinic cohort, including PSP and CBD, than in the community cohort. The Discussion attributes the clinic excess of atypical pathologies to likely selection or referral biases. The paper does not report a separate proportion for non-AD tauopathies as a group, so that more specific characterization is not fully established. (LLM, conf=0.83)
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Duyckaerts et al (287) and Sabbagh et al (252) independently arrived at the conclusion that the density of NFTs in selected cerebral cortical fields significantly (p < 0.01) correlated with Blessed or Mini-Mental State Examination scores (297).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between NFTs and Cognitive Status
What the sources say
- Not checked yetcites [287] source
- Partly supportedcites [252] sourceExperimental — accuracy not yet measured
The Results (page unavailable) report significant correlations between NFT counts and MMSE scores across the regions studied, with strong correlations in the neocortex. Our copy does not establish the specific p < 0.01 threshold for those correlations. Sabbagh et al. measured MMSE, not the Blessed scale; the sentence attributes the Blessed-or-MMSE finding jointly to two studies. (LLM, conf=0.84)
- Not checked yetcites [297] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In fact, there have been hints of some beneficial effects (clinical and biochemical) linked to human anti-Aβ immunotherapies (74-79).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“On the other hand, the density of tau-positive NPs does correlate directly and statistically independently with some degree of cognitive impairment (105-107) (Fig. 2).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“We are aware of no reported case of truly intact cognition despite extremely severe AD pathologic changes (i.e. widespread neocortical NFTs) measured with quantitative pathologic analysis, although many persons with intact cognition have been assessed in autopsy series (33, 42, 54, 133, 142, 148, 151-166).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Even in extreme old age, the presence of many neocortical NFTs correlates with antemortem cognitive decline (105, 188-191).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AD-Related Brain Pathology in Individuals Older Than 90 Years
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Although the study designs were diverse in CPC studies involving AβPs, most studies confirm a significant correlation between antemortem cognitive impairment and neocortical AβPs, as demonstrated by Blessed et al (254) (Fig. 3).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between AβPs and Cognitive Status
What the sources say
- Not checked yetcites [254] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“A recent study with large numbers of subjects assessed with standardized antemortem cognitive testing found that the amyloid stage that has progressed to involve the striatum is highly predictive of dementia (263).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between AβPs and Cognitive Status
What the sources say
- Not checked yetcites [263] Beach, 2012, Striatal amyloid plaque density predicts braak neurofibrillary stage and clinicopathological Alzheimer's disease: Implications for amyloid imaging, J Alzheimers Dis source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- It may state two separate claims as one. 53
- Probably not a substantial claim. 21
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Furthermore, diffuse AβPs may be associated with cerebral amyloid angiopathy, which could produce impairments separately (103, 104), although see Nelson et al (105).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [103] source
- Partly supportedcites [104] sourceExperimental — accuracy not yet measured
The Abstract Results and Discussion report that CAA is associated with Alzheimer’s disease pathology and that more severe CAA is associated with lower performance in specific cognitive domains after accounting for that pathology. The Methods include diffuse plaques in the measure of Alzheimer’s disease pathology, but the paper does not establish an association between diffuse Aβ plaques specifically and CAA. Page numbers are unavailable in our copy. (LLM, conf=0.83)
- Not checked yetcites [105] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
Every source the paper cites for this claim was checked and supports it.
In the paper
“It is expected that many persons die with brains that exhibit AD neuropathologic change in the preclinical phase of AD; indeed, data support the modeled expectations (44, 142).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
- Supportedcites [44] source
The Introduction describes 2,332 nonselected autopsy cases, and the Discussion says pretangle pathology in people without clinically manifest AD may mark a condition leading to clinical disease. The reported autopsy findings support the cited point that people can die with AD-associated pathology before clinical AD; the modeled expectation is the citing authors’ framing. (LLM, conf=0.87)
- Supportedcites [142] source
The section on the clinical context of AD says that many people with AD-related pathology die with minimal or no detectable cognitive deficits and that theoretical and empirical data agree. The Figure 4 caption in Summary and Conclusions states that empirical data confirm the prediction that many people die with appreciable AD-type pathology before dementia begins. (LLM, conf=0.95)
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Supported
In the paper
“The findings reported by Tomlinson et al (38) in 1970 have been replicated many times: “[NFTs are] found in both controls and dements [demented subjects] in the hippocampus, but elsewhere in the cortex was only severe or widespread in the dements; severe generalized neurofibrillary change in the cortex was not seen in any control; it seems possible that its occurrence always indicates dementia.””
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
- Not checked yetcites [38] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
In the paper
“There were 58 subjects with dementia and AD changes, of which 40 had 2 or more neocortical tangles per high-magnification field in frontal, temporal, and parietal lobes; 18 had no neocortical NFTs.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [101] source
plainn = 58- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The cases did not differ in hippocampal tangle densities and had no significant differences in brain weights, neocortical thickness, or neocortical neuron counts.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [101] source
plainn = 58- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“There have been cases in which individuals with mid- to late-stage clinical AD were administered anti-Aβ immunotherapy that partially cleared AβPs, but this clearance did not seem to mitigate NFT formation or the inexorable disease course (69-71).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Despite this, both groups were demented and did not differ significantly on the Blessed Dementia Scale.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [101] source
plainn = 58- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Using data from the National Alzheimer’s Coordinating Center with inclusion and exclusion criteria, as described previously (282), NPs and NFTs tend to coexist (Table 4); this corroborates earlier observations (283).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Neuritic AβP (NP): A Pathologic Entity With Mechanistic Implications
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“In sum, both clinical and pathologic assessments are imperfect, variably applied, and constantly evolving.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > OVERVIEW OF CHALLENGES TO CPC STUDIES IN AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: unclear — It is unclear whether it could be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Both clinical and pathologic assessments are imperfect, variably applied, and constantly evolving.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although Aβ plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates best with the burden of neocortical neurofibrillary tangles.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > Abstract
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Studies on human subjects with autopsy confirmation entail numerous potential biases that affect both their general applicability and the validity of the correlations.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Additional changes that may also occur in the brains of AD patients include amyloid angiopathy, age-related brain atrophy, synaptic pathology, white matter rarefaction, granulovacuolar degeneration, neuron loss, TDP-43 proteinopathy, and neuroinflammation (20-26), which may contribute to cognitive impairment; however, these are not considered pathognomonic features of AD (3).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
- Not checked yetcites [20] source
- Not checked yetcites [21] source
- Not checked yetcites [22] Masliah, 1995, Mechanisms of synaptic dysfunction in Alzheimer's disease, Histol Histopathol
- Not checked yetcites [23] source
- Not checked yetcites [24] source
- Not checked yetcites [25] source
- Not checked yetcites [26] Scheff, 2006, Alzheimer's disease-related alterations in synaptic density: Neocortex and hippocampus, J Alzheimers Dis source
- Not checked yetcites [3] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The tendency to dichotomize the disease (i.e. “demented vs nondemented”) and overreliance on ordinal variables may also obscure important relationships.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > OVERVIEW OF CHALLENGES TO CPC STUDIES IN AD
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, CPC studies rarely are a random sample of the population and clinic- and hospital-based CPCs are subject to other potential biases.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > OVERVIEW OF CHALLENGES TO CPC STUDIES IN AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: CPC studies rarely are a random sample of the population.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As such, neurofibrillary degeneration restricted to subcortical sites is often subclinical, whereas widespread neocortical NFTs are almost always associated with severe cognitive impairment in more than 1 disease state.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“On the other hand, tau gene mutations can produce clinical dementia with NFTs; this indicates that, under some conditions, NFTs may be directly linked to the primary or at least proximal neurodegenerative changes (29, 31, 37).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Neurofibrillary tangles are not specific for AD (29-32); indeed, they are found in almost every class of brain disease and are universal (yet topographically restricted) in normal aging subjects (33).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
- Not checked yetcites [29] source
- Not checked yetcites [30] Arai, 2001, Distinct isoforms of tau aggregated in neurons and glial cells in brains of patients with Pick's disease, cor-ticobasal degeneration and progressive supranuclear palsy, Acta Neu-ropathol source
- Not checked yetcites [31] source
- Not checked yetcites [32] source
- Not checked yetcites [33] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“This subset of AβPs is a hallmark of the current diagnostic criteria for AD, although there is no universally accepted definition of a NP.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The concordance of genetics and Aβ deposition is aligned with CPC studies that indicate that AβPs may be a temporally “upstream” feature of the neocortical disease, with the caveats that brainstem and medial temporal lobe pretangles and NFTs are seen in subjects without Aβ deposition in all age categories (33, 39, 44).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In contrast to NFTs, AβPs are extracellular (45, 46) and are found in a high proportion of all elderly persons but are not universal (44, 47, 48).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Both the density and the neuroanatomic localization of NFTs are important parameters in AD neuropathology.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It must be acknowledged that a simplistic conceptualization of “plaques and tangles” does not adequately reflect the complexity of the biochemical changes in the brains of patients with AD.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
plain- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is clear, as mentioned previously, that AβPs, in the absence of any other neurodegenerative disease lesions or other pathologies, are not a sufficient substrate for severe dementia and thus do not constitute “advanced AD pathologic changes.””
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
boosted- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“There are multiple reasons why these trials may have failed, including the late timing of the therapy. Thus, conclusions drawn from these trials may be premature (72, 73).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“As for Assertion 2, it is true that dementia, even one that may be clinically similar to probable AD, may be present without AD pathologic changes; this is simply not AD, but presumably one among many other diseases that cause dementia (e.g. hippocampal sclerosis or vascular dementia).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These patterns of brain changes indicate specific features that can be correlated with clinical parameters, modeled to understand disease mechanisms, and targeted for therapeutics.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Because autopsies provide only cross-sectional data, they cannot prove mechanism.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Thus, AβPs and NFTs are the hallmark features of AD but do not develop in the human brain according to the same temporal or anatomic pattern (60, 61).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > AβPS AND NEUROFIBRILLARY TANGLES: THE HISTOPATHOLOGIC HALLMARKS LINKED TO AD
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, peptides and higher-order aggregates derived from products of APP and MAPT genes can potentially lead to combinations of neuroprotective and toxic attributes.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
In the paper
“In contrast, dense and extensive neocortical NFTs are very consistently associated with dementia and thus, according to new diagnostic criteria, these are required to constitute high burden of AD neuropathologic change (3).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
- Not checked yetcites [3] source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The toxicity of oligomeric forms of tau and Aβ peptides could be connected with biochemical changes that also produce NPs and NFTs; thus, the oligomeric species may be directly related to the neuropathology, although they are not exactly correlated (90-95).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
What the sources say
- Not checked yetcites [90] source
- Not checked yetcites [91] Jin, 2011, Soluble amyloid {β}-protein dimers isolated from Alzheimer cortex directly induce Tau hyperphosphorylation and neuritic degeneration, Proc Natl Acad Sci U S A source
- Not checked yetcites [92] Gadad, 2011, Targeting oligomers in neurodegenerative disorders: lessons from alpha-synuclein, tau, and amyloid-β peptide, J Alzheimers Dis source
- Not checked yetcites [93] source
- Not checked yetcites [94] source
- Not checked yetcites [95] source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Since both tau phosphorylation and Aβ peptide generation are seen in “normal” brains, some contend that there are probably beneficial and adaptive aspects to these molecular processes.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CONTROVERSIES IN AD CPC RESEARCH
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“When modern pathologic methods are used, severe cognitive impairment associated only with diffuse AβPs in the brain at autopsy is rare and has an unknown relationship to AD.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The median life expectancy in Western countries is approximately 79 years (141).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
- Not checked yetcites [141] Central Intelligence Agency. The World Factbook. Washington, DC: Central Intelligence Agency, 2008
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
In the paper
“There are also some individuals with intact or subtly diminished cognitive abilities whose brains harbor hippocampal and/or amygdala NFTs (Braak stages III–IV) with few or no AβPs; these represent approximately 5% of cases in some large autopsy series (41).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Tangle-Only” or “Tangle-Predominant” Dementia and Other Non-AD Tauopathies
What the sources say
- Not checked yetcites [41] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“Subtle cognitive impairment may be associated with diffuse AβPs, indicating that these lesions may play a direct role in incipient AD (54), although a direct role of diffuse Aβ plaques without tau pathology has not been proven.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [54] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“The current revision of the National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of AD stipulate that subjects with moderately dense neuritic AβPs may be regarded as having an intermediate level of AD neuropathologic change and that other potential contributors to cognitive impairment and dementia should be sought (3).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Plaque-Only” Dementia
What the sources say
- Not checked yetcites [3] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, this is precisely the observation reported by one of the largest autopsy series to date (142) and is well supported by AD biomarker studies (143-145).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, using these data, we can deduce confidently that an “average” person dying at age 79 has an approximately 15% likelihood of having been diagnosed clinically with ADD, but an approximately 30% to 40% chance of harboring significant AD neuropathologic changes (otherwise, the prevalence of ADD could not reach approximately 30%–40% by age 95).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In this condition, the NFTs comprise tau isoforms similar to those of classic AD, but these subjects do not have the same distribution of APOE genotypes as subjects with AD (118).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Tangle-Only” or “Tangle-Predominant” Dementia and Other Non-AD Tauopathies
What the sources say
- Not checked yetcites [118] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“In most community-based autopsy series, non-AD tauopathies constitute approximately 1% of dementia cases (108-115) (but see Noda et al [116]).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > “Tangle-Only” or “Tangle-Predominant” Dementia and Other Non-AD Tauopathies
What the sources say
- Not checked yetcites [108] source
- Not checked yetcites [109] source
- Not checked yetcites [110] source
- Not checked yetcites [111] Schneider, 2009, The neuropathology of older persons with and without dementia from community versus clinic cohorts, J Alzheimers Dis source
- Not checked yetcites [112] source
- Not checked yetcites [113] source
- Not checked yetcites [114] source
- Not checked yetcites [115] source
- Not checked yetcites [116] source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“The prevalence of dementia due to AD, as judged by clinicians, doubles every half-decade after age 65; thus, approximately 30% to 40% of living 95-year-old patients receive the diagnosis of ADD (126-128).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AβPs and NFTs But No Dementia
What the sources say
- Not checked yetcites [126] source
- Not checked yetcites [127] Aronson, 1991, Dementia, Age-dependent incidence, prevalence, and mortality in the old old. Arch Intern Med
- Not checked yetcites [128] Katzman R Kawas C . The epidemiology of dementia and Alzheimer disease. In: Terry RD , ed. Alzheimer Disease. New York, NY: Raven Press, Ltd, 1994:105–22
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“A notable example of this is schizophrenia, which, in elderly patients, is associated with dementia, although the underlying basis of this dementia is enigmatic (174-176).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > Dementia Cases Lacking AβPs, NFTs, or Other Pathologic Substrates
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Cerebrovascular disease (CVD) is the most prevalent non-AD pathologic diagnosis in the brains of the advanced aged and is directly relevant to any CPC study related to dementia.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AD-Related Brain Pathology in Individuals Older Than 90 Years
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Normal pressure hydrocephalus is another poorly understood cause of dementia that may lack AD pathologic changes (177, 178).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > Dementia Cases Lacking AβPs, NFTs, or Other Pathologic Substrates
What the sources say
- Not checked yetcites [177] Leinonen V Koivisto AM Savolainen S . Post-mortem findings in 10 patients with presumed normal pressure hydrocephalus and review of the literature. [published online ahead of print February 10, 2012] Neuropathol Appl Neurobiol
- Not checked yetcites [178] source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, not all studies are in agreement on this point (185, 186); these “survivors” represent a small fraction of the human population with underrepresentation of APOE ε4 allele (187).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AD-Related Brain Pathology in Individuals Older Than 90 Years
What the sources say
- Not checked yetcites [187] source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In the same way, AβPs may be a key pathologic factor in AD without equating with the clinical features of ADD.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between AβPs and Cognitive Status
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Owing in part to the scarcity of neocortical NFTs in the absence of AβPs, and the relatively modest apparent direct impact of AβPs on cognition, it has been suggested that the pathogenetic effect of AβP-related substances may be mediated by “seeding” neurofibrillary pathology (46, 88, 189, 264, 265).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between AβPs and Cognitive Status
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“For this reason, the number of AβPs might plateau (or at least the rate of increase flatten out), leading to a “ceiling effect” relatively early in disease process that confounds linear correlations between plaque number and severity of cognitive change (253).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between AβPs and Cognitive Status
What the sources say
- Not checked yetcites [253] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nevertheless, the profound impact of CVD on studies pertinent to cognition in the elderly seems to be underappreciated in dementia research (208-210).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > LESS-PREVALENT PATTERNS OF CLINICAL AND PATHOLOGIC FEATURES FOUND IN HUMAN BRAINS > AD-Related Brain Pathology in Individuals Older Than 90 Years
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“In more advanced disease, the neuroanatomic distribution of NFTs correlates both with the location at which neurons die (302-305) and with the cognitive domains affected in patients with ADD.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between NFTs and Cognitive Status
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“As AD progresses, the NFTs become numerous in locus coeruleus which may suggest the same pathogenetic process is becoming more severe (301).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between NFTs and Cognitive Status
What the sources say
- Not checked yetcites [301] source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The abnormal NP-contacting dendrites and axons contain pathologic tau fibrils identical to those seen in NFTs (244, 273), with loss of adjacent synapses (274, 275).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Neuritic AβP (NP): A Pathologic Entity With Mechanistic Implications
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Dystrophic axons from completely different afferent sources, expressing distinct neurotransmitters, have been shown to be present in particular NPs (276, 277), which strongly implies that toxicity is directed from the (extracellular) plaque to the radially arranged intracellular neurites.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Neuritic AβP (NP): A Pathologic Entity With Mechanistic Implications
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This process may be synergistic or identical to the stimuli that could promote NFTs in human brains.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Neuritic AβP (NP): A Pathologic Entity With Mechanistic Implications
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: fails — It may be too vague to check against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, some evidence exists for NFT “turnover,” neuronal shrinkage, and/or non-NFT cell death mechanism(s).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > CLINICOPATHOLOGIC CORRELATION IN AD > Correlation Between NFTs and Cognitive Status
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Neurofibrillary tangles are quantified with certainty only at autopsy.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Concomitant pathologies are very common in aging brains.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > SUMMARY AND CONCLUSIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“A patient lacking AD pathologic diagnosis at autopsy, despite “biomarker positivity,” is not an AD case and suggests the biomarker has imperfect specificity.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Neuritic plaques combine extracellular Aβ deposition and intracellular neurofibrillary (tau protein) pathology.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > SUMMARY AND CONCLUSIONS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: fails — The paper may give no reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Indeed, there are still also no recognized biomarker-based criterion standards for a large number of other neurodegenerative tauopathies, synucleinopathies, and vascular brain changes.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Pathologic assessments cannot prove molecular mechanisms; instead, they identify and describe deviations from what is recognized as “normal.””
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Because cognitive impairment in aging may be attributed to many different conditions other than AD, current biomarkers for AD are limited to predicting which patients may become cognitively impaired with neocortical AβPs and NFTs, rather than just predicting cognitive impairment alone.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“However, until such a method becomes available, neuropathologic examination remains the criterion standard for disease definition.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For example, hippocampal atrophy is visualized on magnetic resonance imaging in both AD and hippocampal sclerosis patients and is therefore not a distinct AD biomarker.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This is an important consideration because up to 20% of individuals in advanced age are affected by hippocampal sclerosis that correlates with cognitive impairment independently of AD pathologic diagnosis (105, 211, 321-323).”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although the density of neocortical NFTs and neuritic AβPs on autopsy correlate with the severity of cognitive dysfunction, and the observed results align with a plausible hypothesis, this does not prove that these pathologic hallmarks are proximate to the ultimate neurotoxic species.”
§ Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature > EVOLVING CONCEPTS AND UNANSWERED QUESTIONS
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
Autopsy is required for definitive AD diagnosis.
“Autopsy is required for definitive AD diagnosis, yet autopsy rates are generally low and autopsy inevitably confers a selection bias.”
The paper relies on this without support.
Autopsy rates are generally low.
“Autopsy is required for definitive AD diagnosis, yet autopsy rates are generally low and autopsy inevitably confers a selection bias.”
The paper relies on this without support.
CPC studies rarely are a random sample of the population.
“Furthermore, CPC studies rarely are a random sample of the population and clinic- and hospital-based CPCs are subject to other potential biases.”
The paper relies on this without support.
Most prior studies have concentrated on middle- and upper-income whites.
“Most prior studies have been performed in countries with the most advantageous socioeconomic conditions and have concentrated on middle- and upper-income whites.”
The paper relies on this without support.
Both clinical and pathologic assessments are imperfect, variably applied, and constantly evolving.
“In sum, both clinical and pathologic assessments are imperfect, variably applied, and constantly evolving.”
The paper relies on this without support.
Neurofibrillary tangles are quantified with certainty only at autopsy.
“As with AβPs, NFTs are quantified with certainty only at autopsy.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Numerous studies have linked tau pathology to cognitive decline, with some evidence suggesting it progresses more rapidly than Aβ accumulation and correlates with neuroinflammation, making it a valuable prognostic marker [20, 25–28].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [26]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“VEEV neuropathology shares similarities with AD, a widespread cognitive disorder of aging, including increased astrogliosis, glial nodules, and pathological indicators of neuroinflammation including perivascular cuffing (Nelson et al., 2012; Williams et al., 2023).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Nelson et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Variance in the distribution and burden of tauopathy in AD is closely associated with the clinical phenotype, 13 cognitive deficit, 14 and rate of cognitive decline. 15”
From Alzheimer's disease and its progression reduce pyramidal cell gain and connectivity (2025) · cites this paper as [14]
The cited source says what the claim attributes to it.
In the citing paper
“Histopathologically, AD is characterized by the formation of intraneuronal neurofibrillary tangles consisting of the hyperphosphorylated microtubule protein, tau, and extracellular deposits of plaques of amyloid-β (Aβ), a breakdown product of the transmembrane amyloid precursor protein (APP) [241]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [241]
The cited source says what the claim attributes to it.
In the citing paper
“Recent studies suggest that NFT pathology closely correlates with neurodegeneration and cognitive decline [1, 2].”
From Selective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology (2016) · cites this paper as [2]
In the citing paper
“For example, there is minimal correlation between phases of amyloid deposition and degree of cognitive decline”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Nelson et al., 2012
In the citing paper
“Unlike Aβ, the stage of tau pathology correlates well with progression of cognitive impairment”
From Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019) · cites this paper as Nelson et al., 2012
In the citing paper
“Its tendency to accumulate for years without causing symptomatic disease (i.e., asymptomatic AD or AsymAD) supports this conclusion [35, 36].”
From Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau (2021) · cites this paper as [35]
In the citing paper
“Compared with cortical Aβ plaque, the density and distribution of phosphorylated tau aggregated in NFTs correlate more closely with AD-associated cognitive impairment and neurodegeneration.12,13,14”
From Positron Emission Tomography Imaging With [ 18 F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [14]
In the citing paper
“given that tangle burden is more closely correlated with cortical atrophy and cognitive decline [46]”
From Deep proteomic network analysis of Alzheimer’s disease brain reveals alterations in RNA binding proteins and RNA splicing associated with disease (2018) · cites this paper as [46]
In the citing paper
“The close correlation between tau deposition and cognitive decline (3)”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [3]
In the citing paper
“In AD, tau burden appears to directly correlate with disease progression and cognitive decline (3).”
From Tau reduction prevents neuronal loss and reverses pathological tau deposition and seeding in mice with tauopathy (2017) · cites this paper as [3]
Citations
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282
Hirono, N., Mori, E., Ikejiri, Y., Imamura, T., Shimomura, T., Hashimoto, M., Yamashita, H., & Ikeda, M. (1997) · PubMed · Cited by 21,012
Kok, J. S., Berg, I. J., & Scherder, E. J. A. (2013) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000353441 · Cited by 20,589
Older Adults' Reasons for Using Technology while Aging in Place
Peek, S. T. M., Luijkx, K. G., Rijnaard, M. D., Nieboer, M. E., van der Voort, C. S., Aarts, S., van Hoof, J., Vrijhoef, H. J., & Wouters, E. (2015) · Gerontology · doi:10.1159/000430949 · Cited by 19,852
Sensitivity and False Alarm Rate of a Fall Sensor in Long-Term Fall Detection in the Elderly
Kangas, M., Korpelainen, R., Vikman, I., Nyberg, L., & Jämsä, T. J. (2014) · Gerontology · doi:10.1159/000362720 · Cited by 19,007
Neuropathological stageing of Alzheimer-related changes.
Braak, H., & Braak, E. (1991) · Acta Neuropathologica · doi:10.1007/bf00308809 · Cited by 16,123 · cited 4×
“Braak stages : Braak stages (60) refer to the hypothetically predictable progression of NFT-type pathologic features in the brain during the course of Alzheimer disease (AD).”
BackgroundInfluentialSelf-citationAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Corder, E. H., Saunders, A. M., Strittmatter, W. J., Schmechel, D. E., Gaskell, P. C., Small, G. W., Roses, A. D., Haines, J. L., & Pericak-Vance, M. A. (1993) · Science · doi:10.1126/science.8346443 · Cited by 9,429
The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
Jack, C. R., Bernstein, M. A., Fox, N. C., Thompson, P., Alexander, G., Harvey, D., Borowski, B., Britson, P. J., L. Whitwell, J., Ward, C., et al. (2008) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.21049 · Cited by 4,347
Blessed, G., Tomlinson, B. E., & Roth, M. (1968) · British Journal of Psychiatry · doi:10.1192/bjp.114.512.797 · Cited by 4,117 · cited 3×
“Although the study designs were diverse in CPC studies involving A A Ps, most studies confirm a significant correlation between antemortem cognitive impairment and neocortical A A Ps, as demonstrated by Blessed et al (254) (Fig.”
MethodResult
Research works printed but not linked: 6
- Terry RD Masliah E Hansen LA . Structural basis of the cognitive alterations in Alzheimer disease. In: Terry RD Katzman R Bick KL , eds. Alzheimer Disease. New York, NY: Raven Press, 1994:179–96
- Schneider, 2009, The neuropathology of older persons with and without dementia from community versus clinic cohorts, J Alzheimers Dis, 18, 691, 10.3233/jad-2009-1227 · DOI · Paper page
- 10.1093/brain/awr053 · DOI · Paper page
- 10.1097/60.10.946 · DOI
- 10.1093/brain/awr308 · DOI · Paper page
- 10.1097/60.11.1075 · DOI
Cited by
Sorted by citations
Items 901–1,000 of 1,010
The Irony of Iron: The Element with Diverse Influence on Neurodegenerative Diseases
Lee, S., & Kovács, G. G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084269 · Cited by 30
“Indeed, several post-mortem studies emphasized that tau pathology correlates more with cognitive decline in AD (for a review, see Nelson P et al. [33]).”
BackgroundNeuroglia in cognitive reserve
Verkhratsky, A., & Zorec, R. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02644-z · Cited by 34
Subramanian, S., Savanur, G., & Madhavadas, S. (2016) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2016.12.101 · Cited by 25
Hovakimyan, A., Antonyan, T., Shabestari, S. K., Svystun, O., Chailyan, G., Coburn, M., Carlen-Jones, W., Petrushina, I., Chadarevian, J. P., Zagorski, K., et al. (2019) · Scientific Reports · doi:10.1038/s41598-019-51809-2 · Cited by 27
Dillon, G. M., Henderson, J. L., Bao, C., Joyce, J. A., Calhoun, M. E., Amaral, B., King, K. W., Bajrami, B., & Rabah, D. (2020) · PLoS ONE · doi:10.1371/journal.pone.0228771 · Cited by 26
“In Alzheimer’s patients, the severity of tau pathology, and not amyloid-β, positively correlates with disease progression, cortical atrophy, and cognitive dysfunction [8,9].”
BackgroundHeat therapy: possible benefits for cognitive function and the aging brain
Schulze, A. T. V., Deng, F., Morris, J. K., & Geiger, P. C. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00168.2020 · Cited by 26
“This devastating disease is characterized by worsening memory and social performance and declines in cognitive function (90, 117).”
BackgroundSelf-citationde la Torre, J. C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201165 · Cited by 28
MicroRNAs as Candidate Biomarkers for Alzheimer’s Disease
Kanach, C., Blusztajn, J. K., Fischer, A., & Delalle, I. (2021) · Non-Coding RNA · doi:10.3390/ncrna7010008 · Cited by 25
“Extracellular amyloid-beta (Aβ40–42) peptide deposits in the form of neuritic plaques are the sine qua non for AD diagnosis on brain autopsy; however, the degree of amyloidosis does not correlate with the severity of AD symptoms [4].”
BackgroundRoles of Microglial Ion Channel in Neurodegenerative Diseases
Cojocaru, A., Burada, E., Bălșeanu, A.-T., Deftu, A., Cătălin, B., Popa‐Wagner, A., & Osiac, E. (2021) · Journal of Clinical Medicine · doi:10.3390/jcm10061239 · Cited by 28
“There are several studies claiming that the inflammatory process plays an important role in the disease progression by facilitating amyloid beta (Aβ) deposition, neuronal damage and cognitive deficits [12,13].”
BackgroundAnatomic survey of seeding in Alzheimer’s disease brains reveals unexpected patterns
Stopschinski, B. E., Del Tredici, K., Estill-Terpack, S.-J., Ghebremedhin, E., Yu, F. F., Braak, H., & Diamond, M. I. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01255-x · Cited by 26
Self-citationFDG‐PET markers of heterogeneity and different risk of progression in amnestic MCI
Caminiti, S., Francesco, S. D., Tondo, G., Galli, A., Redolfi, A., & Perani, D. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13385 · Cited by 27
“11 Tau pathology correlates with neuronal and synaptic loss, 12 which is also detectable by 18 F-fluorodeoxyglucose (FDG)-PET brainmetabolism.”
BackgroundAlzheimer’s Disease: Models and Molecular Mechanisms Informing Disease and Treatments
Nystuen, K., McNamee, S. M., Akula, M., Holton, K. M., DeAngelis, M. M., & Haider, N. B. (2024) · Bioengineering · doi:10.3390/bioengineering11010045 · Cited by 28
Meco, A. D., Joshi, Y. B., Lauretti, E., & Praticò, D. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.78 · Cited by 27
Metaflammasome components in the human brain: a role in dementia with Alzheimer's pathology?
Taga, M. F., Minett, T., Classey, J. D., Matthews, F. E., Brayne, C., Ince, P. G., Nicoll, J. A. R., Hugon, J., Boche, D., & CFAS, M. (2016) · Brain Pathology · doi:10.1111/bpa.12388 · Cited by 27
“In contrast, systemic inflammation (3) and tangle pathology (4) correlate closely with cognitive decline, but the underlying biological mechanisms are poorly understood.”
BackgroundCurrent Role for Biomarkers in Clinical Diagnosis of Alzheimer Disease and Frontotemporal Dementia
Sheikh‐Bahaei, N., Sajjadi, S. A., & Pierce, A. L. (2017) · Current Treatment Options in Neurology · doi:10.1007/s11940-017-0484-z · Cited by 28
Cisternas, P., Zolezzi, J. M., Lindsay, C. B., Rivera, D. S., Martinez, A. N., Bozinovic, F., & Inestrosa, N. C. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180729 · Cited by 27
Baghel, V., Tripathi, M., Parida, G. K., Gupta, R., Yadav, S., Kumar, P., Dey, A. B., Damle, N. A., Kumar, R., & Bal, C. (2019) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000002791 · Cited by 26
“Our findings support the hypothesis that regional tau deposition in AD is closely related to cognitive performance.(16) Negative associations between tau retention and cognition were noted in the temporal (among the first to be affected by NFT), parietal (both AD groups), and frontal lobes (in advanced AD groups).”
ResultAlzheimer's Disease: Many Failed Trials, So Where Do We Go from Here?
Reiss, A. B., Glass, A. D., Wısnıewskı, T., Wolozin, B. L., Gomolin, I. H., Pinkhasov, A., Leon, J. D., & Stecker, M. M. (2020) · Journal of Investigative Medicine · doi:10.1136/jim-2020-001297 · Cited by 26
Self-citationJain, S. K., Stevens, C. M., Margret, J. J., & Levine, S. N. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0245 · Cited by 33
Shen, R., Ardianto, C., Celia, C., Sidharta, V. M., Sasmita, P. K., Satriotomo, I., & Turana, Y. (2023) · Dementia & Neuropsychologia · doi:10.1590/1980-5764-dn-2023-0012 · Cited by 31
“Accumulation of A β plaques and NFTs correlated with the progression of memory and cognitive impairment by its cause of neuronal synapse damage, although AD severity is also contributed by multifactorial co-pathology 62,64 .”
BackgroundNeighborhood disadvantage reduces cognitive reserve independent of neuropathologic change
Kim, B.-R., Yannatos, I., Blam, K., Wiebe, D. J., Xie, S. X., McMillan, C. T., Mechanic-Hamilton, D. J., Wolk, D. A., & Lee, E. B. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13736 · Cited by 25
Amygdala atrophies in specific subnuclei in preclinical Alzheimer's disease
Salman, Y., Gérard, T., Huyghe, L., Colmant, L., Quenon, L., Malotaux, V., Ivanoiu, A., Lhommel, R., Dricot, L., Hanseeuw, B. J., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14235 · Cited by 26
“3,4 Based on autopsy 5,6 and imaging 7 studies, the prevailing research hypothesis posits that A β precedes and exacerbates tau pathology, 8 which in turn leads to neurodegeneration in specific brain regions and corresponding cognitive deficits.”
Amyloid-β oligomers increase the binding and internalization of tau oligomers in human synapses
Kadamangudi, S., Marcatti, M., Zhang, W.-R., Fracassi, A., Kayed, R., Limon, A., & Taglialatela, G. (2024) · Acta Neuropathologica · doi:10.1007/s00401-024-02839-2 · Cited by 25
Drug Development in Alzheimer’s Disease: The Contribution of PET and SPECT
Declercq, L., Vandenberghe, R. R., Laere, K. V., Verbruggen, A., & Bormans, G. M. (2016) · Frontiers in Pharmacology · doi:10.3389/fphar.2016.00088 · Cited by 27
“In contrast to the NFTs, however, there is a poor correlation between the extent of these plaques and the degree of cognitive impairment (Nelson et al., 2012), furthermore non-demented individuals can heave substantial loads of Aβ deposition without revealing any clinical symptoms (Villemagne et…”
BackgroundFirst-in-Rat Study of Human Alzheimer’s Disease Tau Propagation
Smolek, T., Jadhav, S., Brezováková, V., Cubinkova, V., Valachova, B., Novák, P., & Žilka, N. (2018) · Molecular Neurobiology · doi:10.1007/s12035-018-1102-0 · Cited by 29
Late Onset Alzheimer’s Disease Risk Variants in Cognitive Decline: The PATH Through Life Study
Andrews, S. J., Das, D., Anstey, K. J., & Easteal, S. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160774 · Cited by 26
“4 analysis suggests that the neuropathological hallmarks of LOAD progress to varying degrees in individuals without dementia and are associated with cognitive status and nonclinical cognitive decline [15,16].”
Tackling gaps in developing life‐changing treatments for dementia
Mauricio, R., Benn, C., Davis, J. B., Dawson, G. R., Dawson, L. A., Evans, A., Fox, N. C., Gallacher, J., Hutton, M., Isaac, J. T. R., et al. (2019) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1016/j.trci.2019.05.001 · Cited by 27
“A long-standing puzzle in AD research has been the finding that there may be a substantial number of Ab plaques in the brain of some individuals who have otherwise normal cognition and conversely people who exhibit phenotypic AD have little or no plaque or tangle deposition [19,20].”
BackgroundNeuroimaging of smell and taste
Olofsson, J., & Freiherr, J. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63855-7.00017-4 · Cited by 26
The Significance of Tau Aggregates in the Human Brain
Castellani, R. J. (2020) · Brain Sciences · doi:10.3390/brainsci10120972 · Cited by 25
“A second observation is that Aβplaques are occasionally abundant in cognitively intact elderly [43,46], while an abundance of neocortical p-tau is reasonably predictive of cognitive dysfunction [45].”
BackgroundSelf-citationNeuropathology of Aging in Cats and its Similarities to Human Alzheimer’s Disease
Sordo, L., Martini, A. C., Houston, E. F., Head, E., & Gunn-Moore, D. A. (2021) · Frontiers in Aging · doi:10.3389/fragi.2021.684607 · Cited by 26
Association of CD2AP neuronal deposits with Braak neurofibrillary stage in Alzheimer’s disease
Camacho, J., Rábano, A., Marazuela, P., Bonaterra‐Pastra, A., Serna, G., Moliné, T., y Cajal, S. R., Martínez-Sáez, E. A., & Hernández‐Guillamón, M. (2021) · Brain Pathology · doi:10.1111/bpa.13016 · Cited by 25
“Indeed, different studies have shown that cognitive decline in AD starts when tau spreads from the entorhinal cortex into the neocortex [18,19], and the stage of tau pathology strongly correlates with the progression of cognitive impairment [14,15,20].”
BackgroundSmirnov, D. S., Salmon, D. P., Galasko, D. R., Goodwill, V., Hansen, L. A., Zhao, Y., Edland, S. D., Léger, G. C., Peavy, G. M., Jacobs, D. M., et al. (2021) · Neurology · doi:10.1212/wnl.0000000000013107 · Cited by 31
“One neuropathologic feature that could contribute to age-related clinical heterogeneity is variation in the distribution of AD pathology.(11,12) Murray et al.”
BackgroundPassive immunization against phosphorylated tau improves features of Huntington's disease pathology
Alpaugh, M., Masnata, M., de Rus Jacquet, A., Lepinay, E., Denis, H. L., Saint-Pierre, M., Davies, P., Planel, E., & Cicchetti, F. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.020 · Cited by 25
Self-citationWalker, J. M., & Richardson, T. E. (2023) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac115 · Cited by 26
Tan, Z., Garduño, B. M., Fernández‐Aburto, P., Chen, L., Ha, N. M.-L., Cogram, P., Holmes, T. C., & Xu, X. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01481-x · Cited by 30
“These findings clearly demonstrate multiple spontaneous AD neuropathologies in the brain of degus with cognitive deficits and are consistent with spontaneous AD in humans that can be correlatively linked to behavioral impairment [48].”
BackgroundCerebral Glucose Metabolism Assessment in Rat Models of Alzheimer’s Disease
Lu, Y., Ren, J., Cui, S., Chen, J., Huang, Y., Tang, C., Shan, B., Nie, B., & Xinsheng, L. (2015) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317515617725 · Cited by 25
Absence of a Role for Phosphorylation in the Tau Pathology of Alzheimer’s Disease
Lai, R. Y. K., Harrington, C. R., & Wischik, C. M. (2016) · Biomolecules · doi:10.3390/biom6020019 · Cited by 24
“In clinico-pathological correlation studies, there is a close relationship between biochemical and histological measures of tau aggregation in post-mortem tissues and deterioration in mental functioning ante mortem [4], a correlation that holds from the earliest detectable stages of mental impairment [5].”
BackgroundXia, C., & Dickerson, B. C. (2017) · PET Clinics · doi:10.1016/j.cpet.2017.02.005 · Cited by 28
Parametric methods for [ 18 F]flortaucipir PET
Golla, S. S. V., Wolters, E. E., Timmers, T., Ossenkoppele, R., van der Weijden, C. W. J., Scheltens, P., Schwarte, L. A., Mintun, M. A., Devous, M. D., Schuit, R. C., et al. (2018) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x18820765 · Cited by 25
Boutajangout, A., Lindberg, H., Awwad, A., Paul, A., Baitalmal, R., Almokyad, I. K., Höidén‐Guthenberg, I., Gunneriusson, E., Frejd, F. Y., Härd, T., et al. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00064 · Cited by 25
Self-citationGireud, M., Reyes‐Esteves, S., Tewari, R., Patrizz, A., Howe, M. D., Kofler, J., Waxham, M. N., McCullough, L. D., & Bean, A. J. (2020) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2020.103542 · Cited by 24
Insights into the pathological basis of dementia from population‐based neuropathology studies
Wharton, S. B., Simpson, J. E., Ince, P. G., Richardson, C. D., Merrick, R. L., Matthews, F. E., Brayne, C., & CFAS (2023) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12923 · Cited by 27
“second CFAS analyses reflects existing studies showing cortical NFT as the strongest pathological associate of dementia.(36,37)”
ResultAngioni, D., Middleton, L. T., Bateman, R. J., Aisen, P. S. S., Boxer, A. L., Sha, S. J., Zhou, J., Gerlach, I., Raman, R., Fillit, H. M., et al. (2025) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100163 · Cited by 27
“Another argument for the potential benefit of anti-amyloid and tau combination therapy is the limited impact of anti-amyloid antibodies [ 3 ], when administered later in the disease course, on measurable biomarkers of tau pathology, which are closely correlated to cognitive decline [ 25 ].”
Herline, K., Prelli, F., Mehta, P. D., MacMurray, C., Goñi, F., & Wısnıewskı, T. (2018) · Alzheimer s Research & Therapy · doi:10.1186/s13195-018-0384-9 · Cited by 24
“It is known that in patients, even at MCI or early AD stages, there is already very extensive Aβ and tau pathology [6, 9, 80].”
BackgroundResultSelf-citationThe Use of Patient-Derived Induced Pluripotent Stem Cells for Alzheimer’s Disease Modeling
Lee, C., Willerth, S. M., & Nygaard, H. B. (2020) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2020.101804 · Cited by 24
Ahmed, T., der Jeugd, A. V., Caillierez, R., Buée, L., Blum, D. L., D’Hooge, R., & Balschun, D. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.570223 · Cited by 24
“Thus, it is Tau pathology and not Aβ-mediated functional deterioration that turned out to correlate better with the severity of dementia (Gomez-Isla et al., 1997; Braak et al., 1998; Nelson et al., 2012; Brier et al., 2016).”
BackgroundThe Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Aggregates
Creekmore, B. C., Chang, Y., & Lee, E. B. (2021) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlab039 · Cited by 28
So, K., Li, A., Liang, Y., Zhang, L., Luo, X., Wu, L.-L., Chen, Z.-W., Wei, G.-H., Zhang, K., Du, Z.-A., et al. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.325012 · Cited by 27
“Interestingly, it is NFTs rather than Aβ plaques that determine cognitive performance in patients with AD (Nelson et al., 2012).”
BackgroundLi, M., Liu, E.-J., Zhou, Q., Li, S., Liu, S., Yu, H., Pan, Q., Sun, F., He, T., Wang, W.-J., et al. (2022) · Military Medical Research · doi:10.1186/s40779-022-00396-x · Cited by 24
“In the brain tissue and cerebrospinal fluid of AD patients, the level of tau protein is approximately 4–8 times that of normal people [5, 6], and the accumulation of hyperphosphorylated tau is positively correlated with the cognitive decline demonstrated by clinicopathologic investigations [7, 8].”
BackgroundGrande, X., Sauvage, M. M., Becke, A., Düzel, E., & Berron, D. (2022) · eLife · doi:10.7554/elife.76479 · Cited by 24
“Tau pathology in Alzheimer’s disease is associated with memory impairment (Bejanin et al., 2017; Berron et al., 2021; Nelson et al., 2012) and information processing might be affected accordingly as reports have shown an association between Alzheimer’s related tau pathology and object memory in early disease stages (B…”
Kotari, V., Southekal, S. S., Navitsky, M. A., Kennedy, I. A., Lu, M., Morris, A., Zimmer, J. A., Fleisher, A., Mintun, M. A., Devous, M. D., et al. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01160-6 · Cited by 25
“Introduction The defining neuropathological hallmarks of Alzheimer’s disease (AD) are an extracellular accumulation of aggregated amyloid-β fragments, typically associated with degenerating neurites (amyloid-β neuritic plaques), and intracellular aggregates of abnormally phosphorylated microtubule-associated tau prote…”
BackgroundRole of microbial dysbiosis in the pathogenesis of Alzheimer's disease
Susmitha, G., & Kumar, R. K. (2023) · Neuropharmacology · doi:10.1016/j.neuropharm.2023.109478 · Cited by 27
Moving Away from Amyloid Beta to Move on in Alzheimer Research
Moreno‐Treviño, M. G., Castillo-López, J., & Meester, I. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00002 · Cited by 24
“Finally, the ABC hypothesis ignores typical characteristics of the disease, such as the spatiotemporal pattern of affected brain areas, the presence of white matter hyperintensities (Kandiah et al., 2015), and vacuolated cells (Nelson et al., 2012).”
BackgroundInfluentialHuang, C., Hsu, S., Tsai, S., Chen, N.-C., Liu, M., Lee, C., Huang, S., Chang, W.-N., Chang, Y., Tsai, W., et al. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0791-z · Cited by 23
“However, it is generally accepted that inflammatory cascades [2] together with neurofibrillary tangles [3] and degenerative neuroimaging biomarkers [4] are more strongly associated with cognitive declines in patients with AD.”
Oligomeric tau-targeted immunotherapy in Tg4510 mice
Schroeder, S. K., Joly‐Amado, A., Soliman, A. S., Sengupta, U., Kayed, R., Gordon, M. N., & Morgan, D. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0274-6 · Cited by 24
“Tau is an attractive target to treat because the progressive pathology of the protein highly correlates with AD symptoms [2, 3].”
Naphthalene-triazolopyrimidine hybrid compounds as potential multifunctional anti-Alzheimer’s agents
Umar, T., Gusain, S., Raza, M. K., Shalini, S., Kumar, J., Tiwari, M., & Hoda, N. (2019) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2019.06.004 · Cited by 26
Malpas, C. B., Sharmin, S., & Kalinčík, T. (2020) · International Journal of Neuroscience · doi:10.1080/00207454.2020.1758087 · Cited by 25
Chandupatla, R., Flatley, A., Feederle, R., Mandelkow, E., & Kaniyappan, S. (2020) · Alzheimer s & Dementia Translational Research & Clinical Interventions · doi:10.1002/trc2.12097 · Cited by 23
“Lysotracker dye stained the lysosomes (image 1, 4).”
Boyton, I., Valenzuela, S. M., Collins‐Praino, L. E., & Care, A. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.11.004 · Cited by 23
Chen, M. W., Ren, X., Song, X., Qian, N., Ma, Y., Yu, W. H., Yang, L., Min, W., Zare, R. N., & Dai, Y. (2025) · Journal of the American Chemical Society · doi:10.1021/jacs.4c15532 · Cited by 28
Altered Function of Hippocampal CA1 Pyramidal Neurons in the rTg4510 Mouse Model of Tauopathy
Dalby, N. O., Volbracht, C., Helboe, L., Larsen, P. H., Jensen, H. S., Egebjerg, J., & Elvang, A. B. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-131358 · Cited by 23
“[2].”
Neurodegenerative lesions: Seeding and spreading
Duyckaerts, C. J. (2013) · Revue Neurologique · doi:10.1016/j.neurol.2013.07.018 · Cited by 24
Self-citationSheng, C., Peng, W., Chen, Z., Cao, Y., Gong, W., Xia, Z.-A., Wang, Y., Su, N.-X., & Wang, Z. (2016) · BMC Complementary and Alternative Medicine · doi:10.1186/s12906-016-1313-8 · Cited by 24
“Mounting evidence indicates that the severity of memory dysfunction correlates strongly with the presence of beta-amyloid plaques and intracellular tau and neocortical neurofibrillary tangles [5, 6].”
BackgroundWoods, J. J., Skelding, K. A., Martin, K. L., Aryal, R., Sontag, E., Johnstone, D. M., Horvat, J. C., Hansbro, P. M., & Milward, E. A. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.10.014 · Cited by 23
Probing Estrogen Sulfotransferase-Mediated Inflammation with [ 11 C]-PiB in the Living Human Brain
Surmak, A. J., Wong, K. P., Cole, G. B., Hirata, K., Aabedi, A. A., Mirfendereski, O., Mirfendereski, P., Yu, A. S., Huang, S., Ringman, J. M., et al. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190559 · Cited by 22
Tubulin modifying enzymes as target for the treatment of tau-related diseases
Rogowski, K., Hached, K., Crozet, C., & van der Laan, S. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107681 · Cited by 21
Variants inPPP2R2BandIGF2BP3are associated with higher tau deposition
Ramanan, V. K., Wang, X., Przybelski, S. A., Raghavan, S., Heckman, M. G., Batzler, A. J., Kosel, M., Hohman, T. J., Knopman, D. S., Graff‐Radford, J., et al. (2020) · Brain Communications · doi:10.1093/braincomms/fcaa159 · Cited by 23
“Given that cognitive decline in Alzheimer’s disease is more closely related to tau accumulation than to amyloid accumulation (Nelson et al., 2012; Ossenkoppele et al., 2016; Bejanin et al., 2017), understanding why certain individuals may have relatively more resistance (avoidance) or resilience (coping) against tau d…”
BackgroundSite-specific mitochondrial dysfunction in neurodegeneration
Vodičková, A., Koren, S. A., & Wojtovich, A. P. (2022) · Mitochondrion · doi:10.1016/j.mito.2022.02.004 · Cited by 22
Taddei, R. N., Sanchez-Mico, M. V., Bonnar, O., Connors, T. R., Gaona, A., Denbow, D., Frosch, M. P., & Gómez‐Isla, T. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01370-3 · Cited by 23
“While resilient brains with a high burden of AD pathology meeting criteria for high probability of AD at autopsy (moderatefrequent neuritic plaques and tangle Braak stage V-VI) according to NIA-AA guidelines [39] represent only a small subset of outliers [18, 68], the percentage of cognitively unimpaired individuals m…”
BackgroundSelf-citationPathological changes induced by Alzheimer’s brain inoculation in amyloid-beta plaque-bearing mice
Lam, S., Hérard, A., Boluda, S., Petit, F., Eddarkaoui, S., Cambon, K., The Brainbank Neuro-CEB Neuropathology Network, Letournel, F., Martin‐Négrier, M., Faisant, M., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01410-y · Cited by 29
“In humans, during clinically established AD, memory impairment is correlated with neocortical tau pathology and with synaptic alterations but not so directly with Aβ plaque load [2, 18, 29].”
BackgroundSelf-citationOatman, S. R., Reddy, J. S., Quicksall, Z., Carrasquillo, M. M., Wang, X., Liu, C., Yamazaki, Y., Nguyen, T., Malphrus, K. G., Heckman, M. G., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00592-2 · Cited by 27
“This is consistent with the well-established knowledge that NFTs comprising hyper-phosphorylated tau correlate with neuronal loss and severity in AD [103].”
ResultChristensen, G. M., Li, Z., Liang, D., Ebelt, S., Gearing, M., Levey, A. I., Lah, J. J., Wingo, A. P., Wingo, T. S., & Hüls, A. (2024) · Neurology · doi:10.1212/wnl.0000000000209162 · Cited by 27
Are large simple trials for dementia prevention possible?
Whiteley, W. N., Anand, S. S., Bangdiwala, S. I., Bosch, J., Canavan, M. D., Chertkow, H. M., Gerstein, H. C., Gorelick, P. B., O'Donnell, M. J., Paré, G., et al. (2019) · Age and Ageing · doi:10.1093/ageing/afz152 · Cited by 24
“and behavioural deficits, [18] and removal of brain amyloid [assessed by positron emission tomography (PET) or cerebrospinal fluid (CSF) studies] has yet to correlate with clinically meaningful improvements in cognition.”
BackgroundTau-Mediated Dysregulation of Neuroplasticity and Glial Plasticity
Koller, E. J., & Chakrabarty, P. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00151 · Cited by 23
Malpas, C. B., Initiative, A. D. N., Saling, M. M., Velakoulis, D., Desmond, P. M., & O'Brien, T. J. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142643 · Cited by 22
“…pathology are compared directly respective contributions to global cognitive dysfunction A (cid:1) consistently accounts for less variance [9, 10] to accumulate in the mesial temporal region, A (cid:1) deposition begins in basal isocortex before spreading inwards to mesial temporal regions…”
Collateral Damage: Neurological Correlates of Non-Fatal Overdose in the Era of Fentanyl-Xylazine
Todaro, D. R., Volkow, N. D., Langleben, D. D., Shi, Z., & Wiers, C. E. (2024) · Neuroscience Insights · doi:10.1177/26331055241247156 · Cited by 24
Preventing cognitive decline in preclinical Alzheimer's disease
Riedel, W. J. (2014) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.10.002 · Cited by 22
“At microscopic level, AD is characterized by the presence of large numbers of neuritic plaques, neurofibrillary tangles and by neuronal cell loss beginning in the hippocampus [3].”
BackgroundTeipel, S. J., Cavedo, E., Weschke, S., Grothe, M. J., Rojkova, K., Fontaine, G., Dauphinot, L., Gonzalez-Escamilla, G., Potier, M.-C., Bertin, H., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2017.05.016 · Cited by 22
Gold, D., Wisialowski, C., Piryatinsky, I., Malloy, P. F., Correia, S., Salloway, S., Klinge, P. M., Gaudet, C. E., Niermeyer, M. A., & Lee, A. K. W. (2022) · Journal of the International Neuropsychological Society · doi:10.1017/s1355617722000868 · Cited by 22
“…AD status using neuritic plaque counts (e.g., Pomeraniec et al., 2016; Yasar et al., 2017) or baseline levels of total tau/amyloid-beta (Aβ) in CSF, which are weakly correlated AD clinical progression and sensitive to non-neurodegenerative factors (Blennow & Zetterberg, 2015; Nelson et al., 2012).”
MethodPezzotti, G., Adachi, T., Imamura, H., Redolfi‐Bristol, D., Adachi, K., Yamamoto, T., Kanamura, N., Marin, E., Zhu, W., Kawai, T., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713351 · Cited by 23
Microglia internalize tau monomers and fibrils using distinct receptors but similar mechanisms
Falkon, K. F., Danford, L., Kuri, E. G., Esquinca‐Moreno, P., Señeriz, Y. L. P., Smith, S. A., Wickline, J. L., Louwrier, A., McPhail, J. A., Sayre, N. L., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.14418 · Cited by 26
“1,2 The spatiotemporal progression of tau aggregate pathology led to the hypothesis that tau spreads intercellularly, promoting “prion-like” seeding of tau aggregation.”
Advances in PET Imaging of Degenerative, Cerebrovascular, and Traumatic Causes of Dementia
Eisenmenger, L. B., Huo, E. J., Hoffman, J. M., Minoshima, S., Matesan, M. C., Lewis, D. H., Lopresti, B. J., Mathis, C. A., Okonkwo, D. O., & Mountz, J. M. (2015) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2015.09.003 · Cited by 21
Nanobiotechnology in Neurodegenerative Diseases
Jampílek, J., Kráľová, K., Novák, P., & Novák, M. (2019) · Springer eBooks · doi:10.1007/978-3-030-30930-5_4 · Cited by 22
Garcez, M. L., Cassoma, R. C. S., Mina, F., Bellettini‐Santos, T., da Luz, A. P., Schiavo, G. L., Medeiros, E. B., Campos, A. C. B. F., da Silva, S., Rempel, L. C. T., et al. (2020) · Metabolic Brain Disease · doi:10.1007/s11011-020-00647-7 · Cited by 21
Targeting Mitophagy in Alzheimer’s Disease
Jayatunga, D. P. W., Hone, E., Bharadwaj, P., Garg, M. L., Verdile, G., Guillemin, G. J., & Martins, R. N. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191258 · Cited by 25
Tau Protein-Targeted Therapies in Alzheimer’s Disease: Current State and Future Perspectives
Pluta, R. M., & Ułamek-Kozioł, M. (2020) · Exon Publications eBooks · doi:10.36255/exonpublications.alzheimersdisease.2020.ch4 · Cited by 27
“This was perhaps due to the hegemony of the amyloid hypothesis and focus of therapeutic strategies on amyloid, while the focus on tau protein, the main component of neurofibrillary tangles which correlates better with the degree of dementia than amyloid (25) has only emerged in recent years.”
BackgroundKaranth, S. D., Schmitt, F. A., Nelson, P. T., Katsumata, Y., Kryscio, R. J., Fardo, D. W., Harp, J. P., & Abner, E. L. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210293 · Cited by 22
“Also consistent with previous studies was the lack of a strong association between amyloidβ (in the absence of high Braak NFT stages) and cognitive trajectories [43].”
Self-citationThe Spectrum of Alzheimer-Type Pathology in Cognitively Normal Individuals
Walker, J. M., Dehkordi, S. K., Schaffert, J., Goette, W. F., White, C. L., Richardson, T. E., & Zare, H. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220898 · Cited by 26
Zetterberg, H., Lautner, R., Skillbäck, T. B., Rosén, C., Shahim, P., Mattsson, N., & Blennow, K. (2014) · Advances in clinical chemistry · doi:10.1016/b978-0-12-800141-7.00005-x · Cited by 21
Carli, F. D., Dessi, B., Mariani, M., Girtler, N. G., Greco, A., Rodriguez, G., Salmon, L., & Morelli, M. (2014) · Bilingualism Language and Cognition · doi:10.1017/s1366728914000054 · Cited by 22
Koss, D. J., Drever, B. D., Stoppelkamp, S., Riedel, G., & Platt, B. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1273-9 · Cited by 22
Christensen, K. R., Beach, T. G., Serrano, G. E., & Kanaan, N. M. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0675-9 · Cited by 23
“Although a “high” level of ADNC does not predict, with 100% certainty, the presence of dementia, it has been accepted by an international panel of neuropathologists [57] that “intermediate” and “high” ADNC are sufficient to cause cognitive impairment and data suggests the probability of Braak V or VI subjects having d…”
BackgroundSelf-citationYeboah, F., Kim, T., Bill, A., & Dettmer, U. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104543 · Cited by 22
Evidence for Decreased Nucleolar PARP-1 as an Early Marker of Cognitive Impairment
Regier, M., Liang, J., Choi, A. H., Verma, K. C., Libien, J. M., & Hernandez, A. I. (2019) · Neural Plasticity · doi:10.1155/2019/4383258 · Cited by 22
“For instance, although plaques and tangles are necessary for a neuropathologic diagnosis, the extent of these pathologies does not correlate well with cognitive decline early in disease progression [4].”
Molecular basis of chronic neurodegeneration
Agrawal, M. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-809356-6.00026-5 · Cited by 25
Tau assemblies do not behave like independently acting prion-like particles in mouse neural tissue
Mukadam, A. S., Miller, L. V. C., Durrant, C. S., Vaysburd, M. J., Katsinelos, T., Tuck, B. J., Sanford, S., Sheppard, O., Knox, C., Cheng, S., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01141-6 · Cited by 23
Raj, A. (2021) · Brain Connectivity · doi:10.1089/brain.2020.0905 · Cited by 21
“The validation of pathology spread models using MRI-derived atrophy assumes that two are colocalized; this is limiting yet reasonable, as tau appears strongly associated with degeneration (Arriagada et al., 1992; Nelson et al., 2012; Xia et al., 2017).”
Future Directions in Imaging Neurodegeneration
Masdeu, J. C. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0718-1 · Cited by 22
Weuve, J. (2014) · American Journal of Epidemiology · doi:10.1093/aje/kwu153 · Cited by 22
Continuous Monitoring of Tau-Induced Neurotoxicity in Patient-Derived iPSC-Neurons
Oakley, D. H., Klickstein, N., Commins, C., Chung, M., Dujardin, S., Bennett, R. E., Hyman, B. T., & Frosch, M. P. (2021) · The Journal of Neuroscience · doi:10.1523/jneurosci.2590-20.2021 · Cited by 18
Self-citation
Metadata
- Authors
- Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., Duyckaerts, C., Frosch, M. P., Haroutunian, V., Hof, P. R., Hulette, C. M., Hyman, B. T., Iwatsubo, T., Jellinger, K. A., Jicha, G. A., Kövari, E., Kukull, W. A., Leverenz, J. B., Love, S., Mackenzie, I. R., Mann, D. M., Masliah, E., McKee, A. C., Montine, T. J., Morris, J. C., Schneider, J. A., Sonnen, J. A., Thal, D. R., Trojanowski, J. Q., Troncoso, J. C., Wisniewski, T., Woltjer, R. L., & Beach, T. G.
- Affiliations
- University of Kentucky (US)
- Uppsala University (SE)
- Northwestern University (US)
- University of Geneva (CH)
- University of Maryland, Baltimore (US)
- University of British Columbia (CA)
- Albert Einstein College of Medicine (US)
- Harvard University (US)
- Boston University (US)
- Rush University Medical Center (US)
- Corresponding author
- Nelson, Peter T.
- ORCID
- Nelson, Peter T.
- Alafuzoff, Irina
- Bigio, Eileen H.
- Braak, Heiko
- Castellani, Rudolph J.
- Davies, Peter
- Tredici, Kelly Del
- Duyckaerts, Charles
- Frosch, Matthew P.
- Haroutunian, Vahram
- Hof, Patrick R.
- Hyman, Bradley T.
- Iwatsubo, Takeshi
- Jellinger, Kurt A.
- Jicha, Gregory A.
- Kukull, Walter A.
- Leverenz, James B.
- Love, Seth
- Mackenzie, Ian R.
- Mann, David M.
- Masliah, Eliezer
- McKee, Ann C.
- Montine, Thomas J.
- Morris, John C.
- Schneider, Julie A.
- Sonnen, Joshua A.
- Thal, Dietmar R.
- Trojanowski, John Q.
- Troncoso, Juan C.
- Woltjer, Randall L.
- Beach, Thomas G.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05
- Volume
- 71
- Issue
- 5
- Pages
- 362-381
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3560290
- OpenAlex
- W2074274706
- Semantic Scholar
- bce678baa6d56ad7c06197507d7903b6c7619507
- Cited by
- 2,050
- References
- 369
- Citations by year
- 2026: 115 · 2025: 153 · 2024: 166 · 2023: 161 · 2022: 213 · 2021: 205 · 2020: 194 · 2019: 179 · 2018: 139 · 2017: 134 · 2016: 108 · 2015: 95 · 2014: 98 · 2013: 72 · 2012: 17
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association
- Alzheimer Forschung Initiative
- Alzheimer's Society
- Deutsche Forschungsgemeinschaft
- Medical Research Council
- National Institute on Aging (AG-028383, AG 016976, AG-15819, AG13854, AG 10161, R01AG035071, AG-02219, AG 05136, P30AG028383, AG008017, U01AG006781, AG 05138, U01AG016976, P50AG005138, AG-06647, AG035071, P30AG010124, AG 05681, R01AG015819, P30AG008017, AG-10124, P30AG010161, R37AG022102, R01AG006647, P30AG008051, AG 08051, P50AG005681, R01AG022102, P50AG005136, P30AG013854, U19AG010483, R37AG006647, R01AG020245, P01AG002219, RF1AG015819)
- National Institute of Neurological Disorders and Stroke (R01NS073502)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, clinicopathological correlation, cognitive impairment, amyloid plaques, neurofibrillary tangles, disease severity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Humans, Statistics as Topic, Amyloid beta-Peptides, Neurofibrillary Tangles, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
