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 701–800 of 1,010
Kok, F. K., van Leerdam, S., & de Lange, E. C. M. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-210607 · Cited by 46
“Nelson et al. (2012) reviewed the validity of the clinical-pathological correlation in AD thereby focusing on neuropathological (A (cid:2) and tau) changes and cognitive impairment using Mini-Mental State Examination (MMSE) scores [74].”
Causal links among amyloid, tau, and neurodegeneration
Bilgel, M., Wong, D. F., Moghekar, A., Ferrucci, L., Resnick, S. M., & Initiative, T. A. D. N. (2022) · Brain Communications · doi:10.1093/braincomms/fcac193 · Cited by 38
“(1) To what extent is neocortical tau accumulation driven by Aβ versus MTL tau pathology? As expected based on the visual assessment of the relationship between EC tau and ITG tau by amyloid status (Fig.”
LATE-NC aggravates GVD-mediated necroptosis in Alzheimer’s disease
Koper, M. J., Tomé, S. O., Gawor, K., Belet, A., Schoor, E. V., Schaeverbeke, J. M., Vandenberghe, R. R., Vandenbulcke, M., Ghebremedhin, E., Otto, M., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01432-6 · Cited by 42
“5, orange arrow) that is considered a crucial degenerative process promoting neuronal atrophy and cognitive decline in AD [52, 68].”
BackgroundSelf-citationSARS-CoV-2 infection increases the gene expression profile for Alzheimer’s disease risk
Green, R. J., Mayilsamy, K., McGill, A. R., Martinez, T. E., Chandran, B., Blair, L. J., Bickford, P. C., Mohapatra, S. S., & Mohapatra, S. (2022) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2022.09.007 · Cited by 42
Smith, C. J., Ashford, J. W., & Perfetti, T. A. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181089 · Cited by 40
Healthy Lifestyle and Cognition: Interaction between Diet and Physical Activity
Serra, M. C., Dondero, K. R., Larkins, D., Burns, A., & Addison, O. R. (2020) · Current Nutrition Reports · doi:10.1007/s13668-020-00306-4 · Cited by 43
Deleterious Alteration of Glia in the Brain of Alzheimer’s Disease
Kim, E., Otgontenger, U., Jamsranjav, A., & Kim, S. S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186676 · Cited by 42
“Like the pathological conversion of Aβ, hyperphosphorylated tau oligomer causes microtubule collapse then forms neurofibrillary tangle (NFT), leading to brain atrophy and cognitive decline [39].”
BackgroundLorenzo, D. D. (2024) · ChemMedChem · doi:10.1002/cmdc.202400180 · Cited by 46
Morphological and Molecular Profiling of Amyloid-β Species in Alzheimer’s Pathogenesis
Almeida, Z. L., Vaz, D. C., & Brito, R. M. M. (2024) · Molecular Neurobiology · doi:10.1007/s12035-024-04543-4 · Cited by 49
“Cognitive decline generally correlates better with NFT burden rather than Aβ plaques [51].”
Alzheimer's Disease Modeling: Ups, Downs, and Perspectives for Human Induced Pluripotent Stem Cells
Wojda, U., & Kuźnicki, J. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-121984 · Cited by 40
“The main hallmarks of AD in the brain are extracellular amyloid- (A ) plaques (senile plaques) and intracellular neurofibrillary tangles (NFTs) [3–6].”
Invited review: Drug development for tauopathies
Grüninger, F. (2014) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12192 · Cited by 40
Unfolded Protein Response and Macroautophagy in Alzheimer’s, Parkinson’s and Prion Diseases
Milisav, I., Šuput, D., & Ribarič, S. (2015) · Molecules · doi:10.3390/molecules201219865 · Cited by 42
“According to post-mortem reports, NFTs are highly associated with neuronal loss and the severity of cognitive decline [167,168], while Aβ plaques appear at the presymptomatic stage and their levels stabilize relatively early in the disease process [169].”
BackgroundHeinisch, J. J., & Brandt, R. (2016) · Microbial Cell · doi:10.15698/mic2016.04.489 · Cited by 41
The Effects of Soluble A.β Oligomers on Neurodegeneration in Alzheimer's Disease
Brouillette, J. (2014) · Current Pharmaceutical Design · doi:10.2174/13816128113199990498 · Cited by 39
“During the progression of the illness, synapse and cell losses gradually become more widespread to ultimately encompass the whole cortex [92-94].”
BackgroundThe Role of Apolipoprotein E Isoforms in Alzheimer’s Disease
Roda, A. R., Montoliu‐Gaya, L., & Villegas, S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180740 · Cited by 41
“Accordingly, although A (cid:2) plaques may play a key role in AD pathogenesis, the severity of cognitive impairment correlates better with the burden of neocortical neurofibrillary tangles and cerebrospinal fluid (CSF) tau levels [10].”
Neuropathological correlates of structural and functional imaging biomarkers in 4-repeat tauopathies
Spina, S., Brown, J. A., Deng, J., Gardner, R. C., Nana, A. L., Hwang, J.-H. L., Gaus, S. E., Huang, E. J., Kramer, J. H., Rosen, H. J., et al. (2019) · Brain · doi:10.1093/brain/awz122 · Cited by 40
Epilepsy in Neurodegenerative Dementias: A Clinical, Epidemiological, and EEG Study
Arnaldi, D., Donniaquio, A., Mattioli, P., Massa, F., Grazzini, M., Meli, R., Filippi, L., Grisanti, S. G., Famà, F., Terzaghi, M., et al. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-191315 · Cited by 39
Brain Tau Imaging: Food and Drug Administration Approval of 18F-Flortaucipir Injection
Mattay, V. S., Fotenos, A. F., Ganley, C. J., & Marzella, L. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.252254 · Cited by 40
“Evidence shows that the severity of cognitive impairment in AD parallels the level of neocortical NFT pathology (4), and at least a B2 level of tau pathology with coexisting b-amyloid and neuritic plaques is necessary to confer a diagnosis of AD (3).”
BackgroundAlzheimer's Disease: Tau Pathology and Dysfunction of Endocytosis
Ando, K., Houben, S., Homa, M., de Fisenne, M.-A., Potier, M., Erneux, C., Brion, J., & Leroy, K. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.583755 · Cited by 42
“Tau pathology is strongly correlated to functional deficits in AD brains (Nelson et al., 2012).”
BackgroundMorales, L. G. F., Correa‐Basurto, J., & Rosales‐Hernández, M. C. (2021) · Antioxidants · doi:10.3390/antiox10020218 · Cited by 39
“Furthermore, phosphorylated Tau accumulates, forming intraneuronal neurofibrillary tangles (NFTs), which are correlated with the severity of cognitive impairment [108].”
BackgroundTropea, M. R., Puma, D. D. L., Melone, M., Gulisano, W., Arancio, O., Grassi, C., Conti, F., & Puzzo, D. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102154 · Cited by 42
Liu, H., Kim, C., Haldiman, T., Sigurdson, C. J., Nyström, S., Nilsson, K. P. R., Cohen, M. L., Wısnıewskı, T., Hammarström, P., & Safar, J. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.101267 · Cited by 37
“However, there is also strong evidence that pathogenic forms of tau protein are an “executioner,” giving rise to the main disease symptoms (50).”
BackgroundSelf-citationGut dysbiosis and age-related neurological diseases in females
Korf, J. M., Ganesh, B. P., & McCullough, L. D. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105695 · Cited by 43
Single cell transcriptomic profiling of a neuron-astrocyte assembloid tauopathy model
Rickner, H., Jiang, L., Hong, R., O’Neill, N. K., Mojica, C. A., Snyder, B. J., Zhang, L., Shaw, D., Medalla, M., Wolozin, B. L., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-34005-1 · Cited by 43
Kushwah, S., Maurya, N. S., Kushwaha, S. K., Scotti, L., Chawade, A., & Mani, A. (2023) · Current Neuropharmacology · doi:10.2174/1570159x21666230216094353 · Cited by 42
“There is a strong positive correlation between aging and AD risk which cumulatively affect the impact of various risks over the span of a person’s lifetime, including biological factors, psychosocial factors, environmental exposures, and genetic susceptibility [6, 19-21].”
Rescue of impaired late–phase long-term depression in a tau transgenic mouse model
Ahmed, T., Blum, D. L., Burnouf, S., Demeyer, D., Buée‐Scherrer, V., D’Hooge, R., Buée, L., & Balschun, D. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.09.015 · Cited by 45
Emerging Diagnostic and Therapeutic Strategies for Tauopathies
Coughlin, D. G., & Irwin, D. J. (2017) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-017-0779-1 · Cited by 42
Tau-imaging in neurodegeneration
Bischof, G. N., Endepols, H., van Eimeren, T., & Drzezga, A. E. (2017) · Methods · doi:10.1016/j.ymeth.2017.08.003 · Cited by 40
“Several previous neuropathological studies indicated a closer correlation between cognitive decline and tau-pathology, as compared to ß-amyloidpathology in AD [91].”
ResultTau Conformation as a Target for Disease-Modifying Therapy: The Role of Truncation
Novák, P., Cehlár, O., Škrabana, R., & Novák, M. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179942 · Cited by 38
Attempt to Untangle the Prion-Like Misfolding Mechanism for Neurodegenerative Diseases
Sarnataro, D. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19103081 · Cited by 39
“The Aβ deposition and NFTs, once formed, affect large areas of the brain with the progression of AD, which is typified by neuronal loss and neuroinflammation [48].”
Backgroundde Oliveira, J. S., Abdalla, F. H., Dornelles, G. L., Palma, T. V., Signor, C., Bernardi, J., Baldissarelli, J., Lenz, L. S., de Oliveira, V. A., Schetinger, M. R. C., et al. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5090-6 · Cited by 38
Peripheral serum metabolomic profiles inform central cognitive impairment
Wang, J., Wei, R., Xie, G., Arnold, M., Kueider‐Paisley, A., Louie, G., Dehkordi, S. M., Blach, C., Baillie, R., Han, X., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-70703-w · Cited by 38
PET Agents in Dementia: An Overview
van Waarde, A., Marcolini, S., Deyn, P. P. D., & Dierckx, R. (2021) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2020.12.008 · Cited by 39
Devous, M. D., Fleisher, A., Pontecorvo, M. J., Lu, M., Siderowf, A. D., Navitsky, M. A., Kennedy, I. A., Southekal, S. S., Harris, T. S., & Mintun, M. A. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-200808 · Cited by 38
Fenamates as Potential Therapeutics for Neurodegenerative Disorders
Hill, J., & Zawia, N. H. (2021) · Cells · doi:10.3390/cells10030702 · Cited by 37
“Although amyloid appears necessary for cognitive decline, it does not seem to be sufficient, nor does amyloid accumulation correlate well with the degree of cognitive decline [29,43].”
Mechanistic and therapeutic role of Drp1 in the pathogenesis of Alzheimer's disease
Bera, A., Lavanya, G., Reshmi, R., Dev, K., & Kumar, R. K. (2022) · European Journal of Neuroscience · doi:10.1111/ejn.15611 · Cited by 43
Arsenault, D., Dal‐Pan, A., Tremblay, C., Bennett, D. A., Guitton, M. J., Koninck, Y. D., Tonegawa, S., & Calon, F. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.1501-13.2013 · Cited by 39
“It is important to underscore that the causal role of both A and tau neuropathologies in AD remains unclear and relies mostly on correlative clinicopathology (Steinerman et al., 2008; Nelson et al., 2012) or genetic studies (Götz et al.”
BackgroundWhat’s in a Gene? The Outstanding Diversity of MAPT
Ruiz-Gabarre, D., Carnero-Espejo, A., Ávila, J., & García‐Escudero, V. (2022) · Cells · doi:10.3390/cells11050840 · Cited by 39
Tau protein profiling in tauopathies: a human brain study
Lantero‐Rodriguez, J., Camporesi, E., Montoliu‐Gaya, L., Gobom, J., Piotrowska, D., Olsson, M., Matečko‐Burmann, I., Becker, B., Brinkmalm, A., Burmann, B. M., et al. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00741-9 · Cited by 42
“…however, both appear pronouncedly increased in AD, becoming a distinctive characteristic of AD pathology. association between NFT deposition, atrophy, and cognitive deficits in AD [46, 47], several studies have indicated that this type of tau deposits might not represent toxic entities.”
BackgroundThe Maze of APP Processing in Alzheimer’s Disease: Where Did We Go Wrong in Reasoning?
Chen, M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00186 · Cited by 42
“…R&D/151, Bay Pines VA Healthcare System, 10,000 Bay Pines Blvd., Bay Pines, FL 33744, USA ming.chen@va.gov Received: 11 March 2015 Accepted: 28 April 2015 Published: 28 May 2015 Citation: Chen M (2015) The maze of APP processing in Alzheimer’s disease: where did we go wrong in reasoning?”
Mundiñano, I.-C., Hernández, M., DiCaudo, C., Ordóñez, C., Marcilla, I., Tuñón, M. J., & Luquín, M. R. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1144-3 · Cited by 37
Molecular imaging of neuropsychiatric symptoms in Alzheimer's and Parkinson's disease
Hirao, K., Pontone, G. M., & Smith, G. S. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.010 · Cited by 38
Putcha, D., Brickhouse, M. J., Touroutoglou, A., Collins, J. A., Quimby, M., Wong, B., Eldaief, M. C., Schultz, A. P., Fakhri, G. E., Johnson, K. A., et al. (2019) · NeuroImage Clinical · doi:10.1016/j.nicl.2019.101889 · Cited by 37
Davtyan, H., Hovakimyan, A., Kiani Shabestari, S., Antonyan, T., Coburn, M. A., Zagorski, K., Chailyan, G., Petrushina, I., Svystun, O., Danhash, E., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0556-2 · Cited by 37
Quevenco, F. C., Bergen, J. M. G. V., Treyer, V., Studer, S. T., Kagerer, S. M., Meyer, R., Gietl, A. F., Kaufmann, P. A., Nitsch, R. M., Höck, C., et al. (2020) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2020.00046 · Cited by 34
“Our finding of distinct functional impacts of β-amyloid and tau might be consistent with the notion of pathogenic synergism of protein aggregates in aging and neurodegenerative disease (Nelson et al., 2012).”
ResultThe Rhesus Macaque as a Translational Model for Neurodegeneration and Alzheimer’s Disease
Stonebarger, G. A., Bimonte‐Nelson, H. A., & Urbanski, H. F. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.734173 · Cited by 38
Sex-Dependent Effects of Intestinal Microbiome Manipulation in a Mouse Model of Alzheimer’s Disease
Kaur, H., Nookala, S., Singh, S., Mukundan, S., Nagamoto‐Combs, K., & Combs, C. K. (2021) · Cells · doi:10.3390/cells10092370 · Cited by 35
“Human data also indicate that Aβ load does not necessarily correlate with cognitive impairment [39].”
BackgroundSanchez-Varo, R. M., Sánchez‐Mejías, E., Fernandez-Valenzuela, J. J., Castro, V. D., Mejias‐Ortega, M., Gómez-Arboledas, Á., Jiménez, S., Sanchez-Mico, M. V., Trujillo‐Estrada, L., Moreno‐González, I., et al. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.752594 · Cited by 42
Interpretable deep learning of myelin histopathology in age-related cognitive impairment
McKenzie, A. T., Marx, G. A., Koenigsberg, D., Sawyer, M., Iida, M. A., Walker, J. M., Richardson, T. E., Campanella, G. S. V., Attems, J., McKee, A. C., et al. (2022) · Acta Neuropathologica Communications · doi:10.1186/s40478-022-01425-5 · Cited by 36
“There are known barriers related to disease heterogeneity, variation in clinician practices, and cognitive reserve [8,48].”
BackgroundSelf-citationEthell, D. W. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-130659 · Cited by 36
Sweet, R. A., MacDonald, M. L., Kirkwood, C. M., Ding, Y., Schempf, T. A., Jones-Laughner, J., Kofler, J., Ikonomović, M. D., López, O. L., Garver, M. E., et al. (2016) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.056580 · Cited by 36
“Somewhat surprisingly given that interpretation, these subgroups also did not reflect several measures associated with greater synaptic pathology in AD, including illness duration and cognitive status (29), presence of psychosis (30), greater amyloid plaque burden (6, 31), greater neurofibrillary tangle pathology (32)…”
BackgroundNew Pathways Identify Novel Drug Targets for the Prevention and Treatment of Alzheimer’s Disease
Penke, B., Szűcs, M., & Bogár, F. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065383 · Cited by 39
“Moreover, the formation of pTau proved to be the common pathway of different, altered molecular signals [70,78].”
BackgroundLu, L., Guo, L., Gauba, E., Tian, J., Wang, L., Tandon, N., Shankar, M., Beck, S. J., Du, Y., & Du, H. (2015) · PLoS ONE · doi:10.1371/journal.pone.0144068 · Cited by 37
“This result is in agreement with previous studies showing that transient cerebral ischemia doesn't induce Aβ overexpression [36, 47, 48].”
ResultŠerý, O., Hlinecká, L., Povová, J., Bonczek, O., Zeman, T., Janout, V., Ambrož, P., Khan, N. A., & Balcar, V. J. (2016) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2016.01.022 · Cited by 36
White-matter commissures: a clinically focused anatomical review
Lavrador, J. P., Ferreira, V., Lourenço, M., Alexandre, I., Rocha, M., Oliveira, E., Kailaya-Vasan, A., & Neto, L. L. (2019) · Surgical and Radiologic Anatomy · doi:10.1007/s00276-019-02218-7 · Cited by 36
Pan, J., He, R., Huo, Q., Shi, Y., & Zhao, L. (2020) · Neurochemical Research · doi:10.1007/s11064-020-03076-1 · Cited by 40
Therapeutic Targeting Strategies for Early- to Late-Staged Alzheimer’s Disease
Kang, Y. J., Diep, Y. N., Tran, M., & Cho, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21249591 · Cited by 36
Genome-wide association study and functional validation implicates JADE1 in tauopathy
Farrell, K. W., Kim, S., Han, N., Iida, M. A., Gonzalez, E. M., Otero‐García, M., Walker, J. M., Richardson, T. E., Renton, A. E., Andrews, S. J., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02379-z · Cited by 36
Self-citationThe correlation between neuropathology levels and cognitive performance in centenarians
Zhang, M., Ganz, A. B., Rohde, S. K., Lorenz, L. M. C., Rozemüller, A. J. M., van Vliet, K., Graat, M., Sikkes, S. A. M., Reinders, M. J. T., Scheltens, P., et al. (2023) · Alzheimer s & Dementia · doi:10.1002/alz.13087 · Cited by 34
“48,49 In contrast, Thal-A β phase varied widely across centenarians and did not associate with neuropsychological test performance, despite a significant association with Braak-NFT stage.”
BackgroundSuppression of tau propagation using an inhibitor that targets the DK-switch of nSMase2
Bilousova, T. V., Elias, C. J., Miyoshi, E., Alam, M. P., Zhu, C., Campagna, J. J., Vadivel, K., Jagodzinska, B. M., Gylys, K. H., & John, V. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.03.209 · Cited by 35
Inhibition of 14-3-3/Tau by Hybrid Small-Molecule Peptides Operating via Two Different Binding Modes
Andrei, S. A., Meijer, F. A., Neves, J. F., Brunsveld, L., Landrieu, I., Ottmann, C., & Milroy, L. ‐. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00118 · Cited by 35
Therapeutic strategies for targeting neurodegenerative protein misfolding disorders
Scannevin, R. H. (2018) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2018.05.018 · Cited by 37
Bos, I., Vos, S. J. B., Jansen, W. J., Vandenberghe, R. R., Gabel, S., Estanga, A., Ecay‐Torres, M., Tomassen, J., den Braber, A., Lleó, A., et al. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00193 · Cited by 35
“These findings are incongruent with previous findings in individuals with MCI as well as in cognitively normal individuals showing that tau and other neurodegenerative features, rather than Aβ, are associated with cognitive impairment and decline in various cognitive domains (Nelson et al., 2012; Mormino et al., 2014;…”
ResultCurrent and Emerging Pharmacological Targets for the Treatment of Alzheimer’s Disease
Morsy, A., & Trippier, P. C. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190744 · Cited by 36
Huang, L., Zhang, Y., Wang, Y., & Lan, Y. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201037 · Cited by 36
Astrocyte subtype-specific approach to Alzheimer's disease treatment
Sarkar, S., & Biswas, S. C. (2021) · Neurochemistry International · doi:10.1016/j.neuint.2021.104956 · Cited by 35
Guimaraes, M. E. N., Lopez-Blanco, R., Correa, J., Fernandez‐Villamarin, M., Millón, M. B. B., Adami, P. V. M., Morelli, L., Kumar, V., Wempe, M. F., Cuello, A. C., et al. (2021) · ACS Nano · doi:10.1021/acsnano.0c09159 · Cited by 36
Hubbard, E. E., Heil, L. R., Merrihew, G. E., Chhatwal, J. P., Farlow, M. R., McLean, C., Ghetti, B. F., Newell, K. L., Frosch, M. P., Bateman, R. J., et al. (2021) · Journal of Proteome Research · doi:10.1021/acs.jproteome.1c00558 · Cited by 33
Self-citationBarthélemy, N. R., Toth, B., Manser, P. T., Sanabria-Bohórquez, S., Teng, E., Keeley, M., Bateman, R. J., Weimer, R. M., & Wildsmith, K. R. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-210677 · Cited by 34
“generation and cognitive impairment than A plaque density [1].”
BackgroundMicroglial autophagy in Alzheimer’s disease and Parkinson’s disease
Wang, Z., Wang, Q., Li, S., Li, X.-J., Yang, W., & He, D. (2023) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.1065183 · Cited by 35
“In the late stage of human AD, a plenty of neurons are lost in the cortex and hippocampus (Nelson et al., 2012).”
BackgroundDicarlo, M., Pignataro, P., Zecca, C., Dell’Abate, M. T., Urso, D., Gnoni, V., Giugno, A., Borlizzi, F., Zerlotin, R., Oranger, A., et al. (2024) · Annals of Neurology · doi:10.1002/ana.26946 · Cited by 37
“52 In our study, a negative association between CSF irisin and t-tau was revealed, in overall patients and female subgroups.”
BackgroundGalpern, W. R., Triana‐Baltzer, G., Li, L., Kolen, K. V., Timmers, M., Haeverans, K., Janssens, L., Kolb, H. C., Nandy, P., Aida, K., et al. (2024) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2024.163 · Cited by 38
Beach, T., Schneider, J., Sue, L., Serrano, G., Dugger, B., Monsell, S. E., & Kukull, W. (2014) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0000000000000114 · Cited by 37
“This led to the confirmed realization that neuritic plaques have a significant association with dementia and cognitive impairment, whereas diffuse plaques generally do not (20).”
Self-citationThe Current Status of Research on Chronic Traumatic Encephalopathy
Perrine, K. R., Helcer, J., Tsiouris, A. J., Pisapia, D. J., & Stieg, P. E. (2017) · World Neurosurgery · doi:10.1016/j.wneu.2017.02.084 · Cited by 37
“Other neuropathological abnormalities similar to CTE and Alzheimer’s diseases are also found in samples of asymptomatic older adults.(50) Conversely, many subjects who initially presented with the cognitive and behavioral symptoms consistent with a traumatic encephalopathic syndrome were later found to lack the neurop…”
BackgroundLate-onset dementia: a mosaic of prototypical pathologies modifiable by diet and lifestyle
Mattson, M. P. (2015) · npj Aging and Mechanisms of Disease · doi:10.1038/npjamd.2015.3 · Cited by 34
Maphis, N. M., Jiang, S., Binder, J., Wright, C., Gopalan, B., Lamb, B. T., & Bhaskar, K. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00069 · Cited by 33
“A growing number of studies implicate reasonably significant positive correlations between the build-up of NFTs and cognitive impairment in various tau-targeted imaging studies in humans (Nelson et al., 2012; Murray et al., 2015; Brier et al., 2016; Ossenkoppele et al., 2016; Scholl et al., 2016).”
BackgroundZhao, Q., Liu, M., Ha, L., Zhou, Y., & Initiative, A. D. N. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00486 · Cited by 39
Flores‐Muñoz, C., Gómez, B., Mery, E., Mujica, P., Gajardo, I., Córdova, C., López-Espíndola, D., Duran-Aniotz, C. A., Hetz, C. A., Muñoz, P., et al. (2020) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.00046 · Cited by 34
Tanner, J. A., & Rabinovici, G. D. (2020) · Journal of Nuclear Medicine · doi:10.2967/jnumed.120.257824 · Cited by 35
“Clinicopathologic studies have revealed that cognition and clinical state are much more closely related to the distribution and burden of neurofibrillary tangles than to the topography or degree of amyloid plaques (5).”
BackgroundXu, Y., Kong, J., & Hu, P. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.617537 · Cited by 36
“Several studies have suggested A β deposition may be required for the tau accumulation, unlike A β , the stage of tau pathology corresponds well with the phase of cognitive decline, which can serve as a predictor of AD progression (Nelson et al., 2012).”
BackgroundPark, H., Lee, Y., & Chang, K. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.66604 · Cited by 33
“The neuropathological characteristics of AD include deposition of senile plaques due to the accumulation of amyloid β (Aβ), neurofibrillary tangles (NFT) through hyperphosphorylation of tau protein, and neuronal cell loss [1].”
BackgroundA History of Senile Plaques: From Alzheimer to Amyloid Imaging
Beach, T. G. (2022) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlac030 · Cited by 37
Self-citationTang, N., Jiang, R., Wang, X., Wen, J., Liu, L., Wu, J., & Zhang, C. (2017) · Brain Research · doi:10.1016/j.brainres.2016.12.027 · Cited by 34
Li, X., Han, J., Bujaranipalli, S., He, J., Kim, E. Y., Kim, H. Y., Im, J. H., & Cho, W. (2022) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2022.114444 · Cited by 38
Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer’s and Parkinson’s Disease
Gutierrez, B. A., & Limón, A. (2022) · Biomedicines · doi:10.3390/biomedicines10071743 · Cited by 32
Decisive role of Reelin signaling during early stages of Alzheimer’s disease
Krstic, D., Pfister, S., Notter, T., & Knuesel, I. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.04.042 · Cited by 33
Matsumura, K., Ono, M., Yoshimura, M., Kimura, H., Watanabe, H., Okamoto, Y., Ihara, M., Takahashi, R., & Saji, H. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.02.054 · Cited by 33
Sensorineural Organs Dysfunction and Cognitive Decline: A Review Article
Wongrakpanich, S., Petchlorlian, A., & Rosenzweig, A. S. (2016) · Aging and Disease · doi:10.14336/ad.2016.0515 · Cited by 33
“found that Alzheimer’s disease also has amyloid-β protein deposits at medial temporal lobes, which is also olfactory pathway[55, 64].”
BackgroundIn vivo coupling of tau pathology and cortical thinning in Alzheimer's disease
Mak, E., Bethlehem, R. A. I., Romero-García, R., Červenka, S., Rittman, T., Gabel, S., Surendranathan, A., Bevan-Jones, W. R., Passamonti, L., Rodríguez, P. V., et al. (2018) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2018.08.005 · Cited by 35
“However, evidence from postmortem and positron emission tomography (PET) studies has not been able to demonstrate strong associations of amyloid b (Ab) with neuronal loss or disease severity in AD [2,3].”
BackgroundResultGan, J., Tu, Q., Miao, S., et al. (2019) · Aging Clinical and Experimental Research · doi:10.1007/s40520-019-01202-w · Cited by 33
Network substrates of cognitive impairment in Alzheimer’s Disease
Tait, L., Stothart, G., Coulthard, E. J., Brown, J. T., Kazanina, N., & Goodfellow, M. (2019) · Clinical Neurophysiology · doi:10.1016/j.clinph.2019.05.027 · Cited by 34
“Whilst amyloidopathy is also likely important for cognitive changes in AD, this link appears to be less direct, with many studies finding tau burden correlates more strongly with cognitive test scores than amyloid (Nelson et al., 2012) – more specifically, a PET study found that temporal lobe tau burden correlates wit…”
Svenningsson, A. L., Stomrud, E., Insel, P. S., Mattsson, N., Palmqvist, S., & Hansson, O. (2019) · Scientific Reports · doi:10.1038/s41598-019-47638-y · Cited by 34
Katsumata, Y., Fardo, D. W., Bachstetter, A. D., Artiushin, S., Wang, W., Wei, A. L., Brzezinski, L. J., Nelson, B. G., Huang, Q., Abner, E. L., et al. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz116 · Cited by 32
“175 lm; (5) 10 lm z-range; and, (6) channel series.”
BackgroundSelf-citationIntact olfactory memory in the 5xFAD mouse model of Alzheimer’s disease from 3 to 15 months of age
O’Leary, T. P., Stover, K. R., Mantolino, H. M., Darvesh, S., & Brown, R. E. (2020) · Behavioural Brain Research · doi:10.1016/j.bbr.2020.112731 · Cited by 30
Jové, M., Mota‐Martorell, N., Torres, P., Ayala, V., Portero‐Otín, M., Ferrer, I., & Pamplona, R. (2021) · Life · doi:10.3390/life11050388 · Cited by 31
p27, The Cell Cycle and Alzheimer´s Disease
García‐Osta, A., Dong, J., Moreno-Aliaga, M. J., & Ramírez, M. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031211 · Cited by 36
“In the late stage of the disease, the brain function continues to decline and the disease affects the autonomy of these patients [61].”
BackgroundSex Differences for Clinical Correlates of Alzheimer's Pathology in People with Lewy Body Pathology
Bayram, E., Coughlin, D. G., & Litvan, I. (2022) · Movement Disorders · doi:10.1002/mds.29044 · Cited by 36
“In those with both LB and AD pathologies, higher neurofibrillary tangle burden has been associated with lower likelihood of LB dementia clinical diagnosis,(10-12) likely because of associated alterations in cognitive profiles and lower likelihood of having LB core features such as visual hallucinations.(13-15) Sex has…”
BackgroundBullich, S., Mueller, A., Santi, S. D., Koglin, N., Krause, S., Kaplow, J. M., Kanekiyo, M., Roé-Vellvé, N., Perrotin, A., Jovalekic, A., et al. (2022) · Alzheimer s Research & Therapy · doi:10.1186/s13195-022-01048-x · Cited by 32
“As expected from neuropathological data [2], tau positron emission tomography (PET) signal is associated to brain hypometabolism [3], atrophy [4], and cognitive dysfunctions [5] more precisely than amyloid-beta PET.”
BackgroundBiomarkers of Alzheimer’s Disease Risk in Peripheral Tissues; Focus on Buccal Cells
François, M., Leifert, W. R., Martins, R. N., Thomas, P., & Fenech, M. F. (2014) · Current Alzheimer Research · doi:10.2174/1567205011666140618103827 · Cited by 34
“This is achieved by the observation of the extracellular senile plaques 80 and intracellular neurofibrillary tangles in the specific areas of the brain such as the 81 entorhinal cortex and hippocampus [7,8].”
BackgroundAdrenomedullin Contributes to Age-Related Memory Loss in Mice and Is Elevated in Aging Human Brains
Larráyoz, I. M., Ferrero, H., Martišová, E., Gil-Bea, F. J., Ramírez, M. J., & Martı́nez, A. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00384 · Cited by 33
“Pathological accumulation of pTau, which compromises synaptic transmission and neuronal viability by contributing to cytoskeleton collapse, correlates better with the severity of cognitive decline in AD than senile plaques (Nelson et al., 2012).”
Background
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
