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
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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.
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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
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“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
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The Alzheimer’s disease neuroimaging initiative (ADNI): MRI methods
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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
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Cited by
Sorted by citations
Items 401–500 of 1,010
The Use of Tau PET to Stage Alzheimer Disease According to the Braak Staging Framework
Macedo, A. C., Tissot, C., Therriault, J., Servaes, S., Wang, Y.-T., Arias, J. F., Rahmouni, N., Lussier, F. Z., Vermeiren, M. R., Bezgin, G., et al. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.122.265200 · Cited by 99
Amyloid-β dimers in the absence of plaque pathology impair learning and synaptic plasticity
Müller‐Schiffmann, A., Herring, A., Abdel‐Hafiz, L., Chepkova, A. N., Schäble, S., Wedel, D., Horn, A. H. C., Sticht, H., Silva, M. A. D. S., Gottmann, K., et al. (2015) · Brain · doi:10.1093/brain/awv355 · Cited by 86
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79
Interneurons, tau and amyloid-β in the piriform cortex in Alzheimer’s disease
Saiz-Sanchez, D., De la Rosa-Prieto, C., Ubeda-Banon, I., & Martinez-Marcos, A. (2015) · Brain Structure and Function · doi:10.1007/s00429-014-0771-3 · Cited by 79
Apostolova, L. G., Zarow, C., Biado, K., Hurtz, S., Boccardi, M., Somme, J. H., Honarpisheh, H., Blanken, A. E., Brook, J. K., Tung, S., et al. (2015) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2015.01.001 · Cited by 77
“They are not specific for AD and are seen in many other neurodegenerative disorders [24].”
Circulating microRNAs in Alzheimer’s disease: the search for novel biomarkers
Dorval, V., Nelson, P. T., & Hébert, S. S. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00024 · Cited by 81
“The Aβ/tau CSF studies have now shown that, as expected (Nelson et al., 2009), up to one-third of nondemented subjects harbor some AD-type pathology (Nelson et al., 2012).”
Self-citationCaselli, R. J., Beach, T. G., Knopman, D. S., & Graff-Radford, N. R. (2017) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2017.02.011 · Cited by 81
“Correlations between cerebral amyloid levels or its topographical distribution and cognitive deficits have been weak.(107) More recently, tau PET has entered into research applications(108) and topographical patterns of ligand distribution correlate well with clinical deficits.”
Self-citationBacterial DNA promotes Tau aggregation
Tetz, G. V., Pinho, M. A., Pritzkow, S., Méndez, N., Soto, C. A., & Tetz, V. (2020) · Scientific Reports · doi:10.1038/s41598-020-59364-x · Cited by 81
Danis, C., Dupré, E., Zejneli, O., Caillierez, R., Arrial, A., Bégard, S., Mortelecque, J., Eddarkaoui, S., Loyens, A., Cantrelle, F., et al. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.01.009 · Cited by 75
“In AD, the severity of cognitive decline is better correlated with the evolution of NFTs than amyloid deposits 3–5 .”
An update on the interactions between Alzheimer's disease, autophagy and inflammation
Bostancıklıoğlu, M. (2019) · Gene · doi:10.1016/j.gene.2019.04.040 · Cited by 78
The therapeutic landscape of tauopathies: challenges and prospects
Cummings, J. L., González, M. I., Pritchard, M. C., May, P. C., Toledo, L. M., & Harris, G. A. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01321-7 · Cited by 85
“Autopsy studies of patients assessed in life demonstrated a stronger relationship between NFT burden and cognitive decline than between amyloid plaque burden and cognition [3, 69].”
BackgroundLatest advances in cerebrospinal fluid and blood biomarkers of Alzheimer’s disease
Milà‐Alomà, M., Suárez‐Calvet, M., & Molinuevo, J. L. (2019) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756286419888819 · Cited by 81
Rodriguez, G. A., Barrett, G., Duff, K., & Hussaini, S. A. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000851 · Cited by 78
P-tau217 as a Reliable Blood-Based Marker of Alzheimer’s Disease
Lai, R., Li, B., & Bishnoi, R. J. (2024) · Biomedicines · doi:10.3390/biomedicines12081836 · Cited by 81
“…of AD diagnosis is based on postmortem examination of brain tissue for amyloid plaques consisting of amyloid-beta (A β ) peptides and neurofibrillary tangles containing phosphorylated tau (p-tau), in vivo diagnosis can be achieved using cerebrospinal fluid (CSF) or neuroimaging biomarkers [1,3].”
BackgroundSartori, M., Mendes, T., Desai, S., Lasorsa, A., Herledan, A., Malmanche, N., Mäkinen, P., Marttinen, M., Malki, I., Chapuis, J., et al. (2019) · Acta Neuropathologica · doi:10.1007/s00401-019-02017-9 · Cited by 72
Ishiki, A., Okamura, N., Furukawa, K., Furumoto, S., Harada, R., Tomita, N., Hiraoka, K., Watanuki, S., Ishikawa, Y., Tago, T., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0140311 · Cited by 77
“This result is consistent with previous observations showing that NFTs are highly associated with neuronal loss and with the clinical severity of dementia [17,18], and suggests that the progression of tau pathology is a strong determinant of cognitive decline.”
BackgroundResultAll (animal) models (of neurodegeneration) are wrong. Are they also useful?
Ransohoff, R. M. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20182042 · Cited by 83
The extracellular chaperone Clusterin enhances Tau aggregate seeding in a cellular model
Yuste‐Checa, P., Trinkaus, V. A., Riera-Tur, I., Imamoglu, R., Schaller, T., Wang, H., Dudanova, I., Hipp, M. S., Bracher, A., & Hartl, F. U. (2021) · Nature Communications · doi:10.1038/s41467-021-25060-1 · Cited by 78
Rabin, J. S., Nichols, E., Joie, R. L., Casaletto, K. B., Palta, P., Dams-O’Connor, K., Kumar, R. G., George, K. M., Satizábal, C. L., Schneider, J. A., et al. (2022) · Brain · doi:10.1093/brain/awac178 · Cited by 80
Self-citationThe problem of genotype and sex differences in life expectancy in transgenic AD mice
Rae, E. A., & Brown, R. E. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.09.002 · Cited by 85
Glial Draper Rescues Aβ Toxicity in aDrosophilaModel of Alzheimer's Disease
Ray, A., Speese, S. D., & Logan, M. A. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0862-17.2017 · Cited by 79
“One neuropathological feature of Alzheimer’s disease (AD) is the formation of extracellular deposits of insoluble fibrillar amyloid(A ) peptides (Holtzman et al., 2011; Nelson et al., 2012).”
BackgroundNi, R., Ji, B., Ono, M., Sahara, N., Zhang, M.-R., Aoki, I., Nordberg, A., Suhara, T., & Higuchi, M. (2018) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.201632 · Cited by 72
“In line with this mechanistic view, tau abnormalities are known to be tightly associated with neurodegeneration and the emergence of clinical symptoms (3,4), providing a rationale for antitau treatments to modify the disease process (5).”
Background18 F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal
Lee, C. M., Jacobs, H. I. L., Marquié, M., Becker, J. A., Andrea, N. V., Jin, D. S., Schultz, A. P., Frosch, M. P., Gómez‐Isla, T., Sperling, R. A., et al. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-170840 · Cited by 81
“To further understand the influence of potential spill-in of CP FTP signal, we investigated whether associations between HC FTP measurement and Aβ or memory performance can be observed as expected based on the autopsy literature [19, 20], when using an unadjusted HC FTP measure or a HC FTP measure adjusted for CP bind…”
Self-citationRöhr, D., Boon, B. D. C., Schuler, M., Kremer, K., Hoozemans, J. J. M., Bouwman, F. H., El-Mashtoly, S. F., Nabers, A., Großerueschkamp, F., Rozemuller, A. J. M., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01091-5 · Cited by 77
“While it is proposed that Aβ is the initial trigger of pathological processes, NFTs are considered to be the progressive force of the disease [55].”
Backgroundde Vries, L. E., Huitinga, I., Kessels, H. W. H. G., Swaab, D. F., & Verhaagen, J. (2024) · Molecular Neurodegeneration · doi:10.1186/s13024-024-00719-7 · Cited by 85
“This holds in particular for NFTs [11].”
Neurotoxic β-amyloid oligomers cause mitochondrial dysfunction—the trigger for PANoptosis in neurons
Meng, X., Song, Q., Liu, Z., Liu, X., Wang, Y., & Liu, J. (2024) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2024.1400544 · Cited by 84
The Importance of the Validation of M/EEG With Current Biomarkers in Alzheimer's Disease
Maestú, F., Cuesta, P., Hasan, O., Fernández, A., Funke, M. E., & Schulz, P. E. (2019) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2019.00017 · Cited by 78
“, 2001) and its deposits correlates with cognitive impairment (Nelson et al., 2012; Vos et al., 2013; Albert et al., 2018) and network dysfunction (Schultz et al.”
BackgroundZhou, F., Sun, Y., Xie, X., & Zhao, Y. (2023) · Alzheimer s Research & Therapy · doi:10.1186/s13195-023-01254-1 · Cited by 81
“This suggests that while amyloid accumulation may be a key initiator of starting the pathological process, other downstream events such as neuroinflammation [3] and tau accumulation may be the predominant drivers of neurodegeneration [4].”
BackgroundCortese, G. P., & Bürger, C. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.08.027 · Cited by 77
Lu, K. P., Kondo, A., Albayram, Ö., Herbert, M. K., Liu, H., & Zhou, X. Z. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2027 · Cited by 74
Proteomics of neurodegenerative diseases: analysis of human post‐mortem brain
Li, K. W., Ganz, A. B., & Smit, A. B. (2018) · Journal of Neurochemistry · doi:10.1111/jnc.14603 · Cited by 74
Procyanidins and Alzheimer’s Disease
Zhao, S., Zhang, L., Yang, C., Li, Z., & Rong, S. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-1469-6 · Cited by 75
Aggregate-selective removal of pathological tau by clustering-activated degraders
Benn, J., Cheng, S., Keeling, S., Smith, A. E., Vaysburd, M. J., Böken, D., Miller, L. V. C., Katsinelos, T., Franco, C., Dupré, E., et al. (2024) · Science · doi:10.1126/science.adp5186 · Cited by 81
“The E3 ligase tripartite motif – containing protein 21 (TRIM21) degrades antibody-bound proteins in an assembly state – specific manner due to the requirement of TRIM21 RING domain clustering for activation, yet effective targeting of intracellular assemblies remains challenging.”
Iacono, D., Resnick, S. M., O’Brien, R., Zonderman, A. B., An, Y., Pletnikova, O., Rudow, G., Crain, B., & Troncoso, J. C. (2014) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000052 · Cited by 73
“Tau immunoreactivity was measured using 2 different markers: one to measure tau immunoreactivity associated with tangles (tau-NFTs) and another to measure tau immunoreactivity associated with neuropil threads (tau-th) (Fig.”
Self-citationYang, Z., Slavin, M. J., & Sachdev, P. S. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.105 · Cited by 74
Neuritic and Diffuse Plaque Associations with Memory in Non-Cognitively Impaired Elderly
Malek-Ahmadi, M., Perez, S. E., Chen, K., & Mufson, E. J. (2016) · Journal of Alzheimer’s Disease · doi:10.3233/jad-160365 · Cited by 73
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“Although the amount of fibrillar A peptides deposited as senile plaques at autopsy does not correlate with AD cognitive impairment (1), the levels of the soluble forms of the peptide appear to correlate better with the severity of the dementia (2).”
BackgroundAducanumab—Hope or Disappointment for Alzheimer’s Disease
Wojtunik-Kulesza, K., Rudkowska, M., & Orzeł-Sajdłowska, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054367 · Cited by 73
“• Individual differences exist in the ability of inflammatory cells to effectively clear senile plaques in the brain [51].”
Plasma Tau Association with Brain Atrophy in Mild Cognitive Impairment and Alzheimer’s Disease
Deters, K., Risacher, S. L., Kim, S., Nho, K. T., West, J. D., Blennow, K., Zetterberg, H., Shaw, L. M. J., Trojanowski, J. Q., Weiner, M. W., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161114 · Cited by 72
“Both in vivo and postmortem studies have shown that pathological tau is correlated with neurodegeneration, disease severity, and cognitiveimpairment[1].”
BackgroundSelf-citationOssenkoppele, R., Mattsson, N., Teunissen, C. E., Barkhof, F., Pijnenburg, Y. A. L., Scheltens, P., van der Flier, W. M., & Rabinovici, G. D. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.04.011 · Cited by 76
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“All models included age, level of education, AMNART VIQ and clinical status (CN versus MCI/AD).”
BackgroundMethodMunder, T., Pfeffer, A., Schreyer, S., Guo, J., Braun, J., Sack, I., Steiner, B., & Klein, C. (2017) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.25741 · Cited by 74
“A progressive loss of neuronal cells in limbic and associated cortical areas is a hallmark of neurodegenerative diseases such as AD and is associated with cognitive decline and memory loss.(15) Growing patient numbers due to the aging society have caused rising socioeconomic costs.”
Smit, T., Deshayes, N. A. C., Borchelt, D. R., Kamphuis, W., Middeldorp, J., & Hol, E. M. (2021) · Glia · doi:10.1002/glia.23981 · Cited by 71
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“Tau pathology is a major neuropathological hallmark of AD besides amyloid-β and is known to correlate better with cognitive impairment in AD than amyloid-β pathology (6).”
BackgroundPhysiological and Pathophysiological Implications of Synaptic Tau
Regan, P. L., Whitcomb, D. J., & Cho, K. (2016) · The Neuroscientist · doi:10.1177/1073858416633439 · Cited by 75
Absence of Alzheimer Disease Neuropathologic Changes in Eyes of Subjects With Alzheimer Disease
Williams, E. A., McGuone, D., Frosch, M. P., Hyman, B. T., Laver, N., & Stemmer-Rachamimov, A. O. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx020 · Cited by 71
Self-citationBiomarkers of Alzheimer's disease and mild cognitive impairment: A current perspective
Lewczuk, P., Mroczko, B., Fagan, A. M., & Kornhuber, J. (2014) · Advances in Medical Sciences · doi:10.1016/j.advms.2014.11.002 · Cited by 73
“Interestingly, the spatial spread of the Tau pathology in the brain tissue of AD patients correlates with the pattern of the cognitive dysfunctions observed clinically [41].”
BackgroundAstrocytic Tau Deposition Is Frequent in Typical and Atypical Alzheimer Disease Presentations
Nolan, A., Resende, E. D. P. F., Petersen, C., Neylan, K. D., Spina, S., Huang, E. J., Seeley, W. W., Miller, Z., & Grinberg, L. T. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz094 · Cited by 69
“CERAD, Thal, and Braak) fail to explain this clinical heterogeneity (2, 10).”
BackgroundEnrichment and Stratification for Predementia Alzheimer Disease Clinical Trials
Holland, D., McEvoy, L. K., Desikan, R. S., Dale, A. M., & Initiative, A. D. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047739 · Cited by 71
The innate immune system in Alzheimer's disease
Boutajangout, A., & Wisniewski, T. (2013) · International Journal of Cell Biology · doi:10.1155/2013/576383 · Cited by 69
“NFT deposition correlates better with the degree of dementia, compared to the amyloid plaque burden [35].”
BackgroundInterleukin-10 deficiency exacerbates inflammation-induced tau pathology
Weston, L. L., Jiang, S., Chisholm, D., Jantzie, L. L., & Bhaskar, K. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02211-1 · Cited by 69
Distinct effects of beta‐amyloid and tau on cortical thickness in cognitively healthy older adults
Harrison, T. M., Du, R., Klencklen, G., Baker, S. L., & Jagust, W. J. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12249 · Cited by 69
Amidst an amygdala renaissance in Alzheimer’s disease
Stouffer, K. M., Grande, X., Düzel, E., Johansson, M., Creese, B., Witter, M. P., Miller, M. I., Wisse, L. E. M., & Berron, D. (2023) · Brain · doi:10.1093/brain/awad411 · Cited by 72
“They showed significantly higher rates of global amygdala volume loss in subjects converting to MCI or to dementia of the Alzheimer’s type (clinical diagnosis without biomarker confirmation) (6.8% and 11.6% volume loss/year, respectively) than in stable controls (1.5% volume loss/ year).”
BackgroundInfluentialCSF p-tau205: a biomarker of tau pathology in Alzheimer’s disease
Lantero‐Rodriguez, J., Montoliu‐Gaya, L., Benedet, A. L., Vrillon, A., Dumurgier, J., Cognat, E., Brum, W. S., Rahmouni, N., Stevenson, J., Servaes, S., et al. (2024) · Acta Neuropathologica · doi:10.1007/s00401-023-02659-w · Cited by 74
“Interestingly, unlike Thal Aβ stages, Braak stages have been shown to correlate with disease progression and cognitive decline [35, 43].”
BackgroundDeficits in Spontaneous Cognition as an Early Marker of Alzheimer’s Disease
Kvavilashvili, L., Niedźwieńska, A., Gilbert, S. J., & Markostamou, I. (2020) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2020.01.005 · Cited by 74
“Brain Mechanisms of Disrupted Spontaneous Cognition in Early Stages of Alzheimer’s Disease The first signs of neuropathological changes of AD tend to occur in posterior parts of the cortex, with anterior and dorsolateral PFC remaining relatively intact [10,11], resulting in”
BackgroundInfluentialThe three-dimensional landscape of cortical chromatin accessibility in Alzheimer’s disease
Bendl, J., Hauberg, M. E., Girdhar, K., Im, E., Vicari, J. M., Rahman, S., Fernando, M. B., Townsley, K. G., Dong, P., Misir, R., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-022-01166-7 · Cited by 65
Perivascular spaces as a potential biomarker of Alzheimer’s disease
Lynch, M., Pham, W., Sinclair, B., O'Brien, T. J., Law, M., & Vivash, L. E. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1021131 · Cited by 70
“Interestingly this set pattern of progression has also been closely associated with cognitive stage and disease progression long after Aβ has aggregated globally (Figure 2; Braak and Braak, 1991; Nelson et al., 2012; Schöll et al., 2016).”
BackgroundAntibody-DerivedIn VivoImaging of Tau Pathology
Krishnaswamy, S., Lin, Y., Rajamohamedsait, W. J., Rajamohamedsait, H. B., Krishnamurthy, P., & Sigurdsson, E. M. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.2755-14.2014 · Cited by 62
Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease
Phillips, J. S., Das, S. R., McMillan, C. T., Irwin, D. J., Roll, E. E., Da Re, F., Nasrallah, I. M., Wolk, D. A., & Grossman, M. (2018) · Human Brain Mapping · doi:10.1002/hbm.23874 · Cited by 68
Furcila, D., DeFelipe, J., & Alonso‐Nanclares, L. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-180173 · Cited by 73
In vivoimaging reveals reduced activity of neuronal circuits in a mouse tauopathy model
Marinković, P., Blumenstock, S., Goltstein, P. M., Korzhova, V., Peters, F., Knebl, A., & Herms, J. W. (2019) · Brain · doi:10.1093/brain/awz035 · Cited by 63
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“We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core sequence ~tau 258–368 .”
Huang, H.-J., Chen, J.-L., Liao, J.-F., Chen, Y., Chieu, M.-W., Ke, Y.-Y., Hsu, C.-C., Tsai, Y.-C., & Hsieh‐Li, H. M. (2021) · BMC Complementary Medicine and Therapies · doi:10.1186/s12906-021-03426-8 · Cited by 65
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Peptides as Potential Therapeutics for Alzheimer’s Disease
Ribarič, S. (2018) · Molecules · doi:10.3390/molecules23020283 · Cited by 69
Cohen, M. L., Appleby, B. S., & Safar, J. (2016) · Prion · doi:10.1080/19336896.2015.1123371 · Cited by 66
“Utilizing this staging system, prospective studies validated the assertions that limited neurofibrillary degeneration involving the entorhinal cortex was compatible with many years of normal cognition, while similar degeneration involving the limbic system usually manifested as mild cognitive impairment, and neocortic…”
MethodMormino, E. C., Papp, K. V., Rentz, D. M., Schultz, A. P., LaPoint, M. R., Amariglio, R. E., Hanseeuw, B. J., Marshall, G. A., Hedden, T., Johnson, K. A., et al. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.2237 · Cited by 63
“Educational level, y 16 (12-18) 16 (13-18)b 16 (14-18)b 16 (16-18)b”
Prion-like mechanisms in Alzheimer disease
Walker, L. C. (2018) · Handbook of clinical neurology · doi:10.1016/b978-0-444-63945-5.00016-7 · Cited by 67
“The primary tauopathies are disorders in which tau aggregation is the major abnormality (Spillantini and Goedert, 2013; Crary et al., 2014; Kovacs, 2015); in many conditions however, tauopathy is secondary to various types of injury or stress to the brain (Nelson et al., 2012).”
BackgroundInfluentialBos, I., Vos, S. J. B., Schindler, S. E., Hassenstab, J. J., Xiong, C., Grant, E., Verhey, F. R. J., Morris, J. C., Visser, P. J., & Fagan, A. M. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.04.015 · Cited by 68
“This may suggest that tau-related pathology is an important contributor to cognitive impairment [40,41] and could be a potential mediator in the relationship between amyloid, vascular factors, and cognitive decline [42].”
BackgroundSelf-citationMelatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease
Chen, D., Lan, G., Li, R., Mei, Y., Shui, X., Gu, X., Wang, L., Zhang, T., Gan, C., Xia, Y., et al. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00302-4 · Cited by 68
“NFTs are closely related to extensive neuronal loss in AD [4].”
BackgroundGene expression parallels synaptic excitability and plasticity changes in Alzheimer’s disease
Saura, C. A., Parra‐Damas, A., & Enríquez-Barreto, L. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00318 · Cited by 65
Pathogenesis of Alzheimer’s Disease
Castellani, R. J., & Perry, G. L. (2014) · Springer eBooks · doi:10.1007/978-1-4614-5836-4_162 · Cited by 67
Self-citationNeuropathology and cognitive performance in self-reported cognitively healthy centenarians
Ganz, A. B., Beker, N., Hulsman, M., Sikkes, S. A. M., NBB, Scheltens, P., Smit, A. B., Rozemüller, A. J. M., Hoozemans, J. J. M., & Holstege, H. H. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0558-5 · Cited by 69
“This trend is mainly carried by the association of Braak stages for NFTs and higher GVD stages with lower cognitive performance across all tests.”
BackgroundInfluentialFRET-based Tau seeding assay does not represent prion-like templated assembly of Tau filaments
Kaniyappan, S., Tepper, K., Biernat, J., Chandupatla, R., Hübschmann, S., Irsen, S. H., Bicher, S., Klatt, C., Mandelkow, E., & Mandelkow�, E. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00389-1 · Cited by 65
Characterization of tau binding by gosuranemab
Sopko, R., Golonzhka, O., Arndt, J. W., Quan, C., Czerkowicz, J., Cameron, A., Smith, B., Yogapriya, M., Gibbons, G. S., Kim, S., et al. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105120 · Cited by 65
Self-citationMicroglia: Friend and foe in tauopathy
Odfalk, K. F., Bieniek, K. F., & Hopp, S. C. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102306 · Cited by 60
Fichou, Y., Al‐Hilaly, Y. K., Devred, F., Smet‐Nocca, C., Tsvetkov, P. O., Verelst, J., Winderickx, J., Geukens, N., Vanmechelen, E., Perrotin, A., et al. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0682-x · Cited by 67
Adiponectin alleviated Alzheimer‐like pathologies via autophagy‐lysosomal activation
He, K., Nie, L., Ali, T., Wang, S., Chen, X., Liu, Z., Li, W., Zhang, K., Xu, J., Liu, J., et al. (2021) · Aging Cell · doi:10.1111/acel.13514 · Cited by 64
“However, NFT formation is closely related to the cognitive dysfunction of AD (Di et al., 2016; Nelson et al., 2009, 2012; Sadigh- Eteghad et al., 2015; Zhang et al., 2018).”
BackgroundGenes associated with the progression of neurofibrillary tangles in Alzheimer’s disease
Miyashita, A., Hatsuta, H., Kikuchi, M., Nakaya, A., Saito, Y., Tsukie, T., Hara, N., Ogishima, S., Kitamura, N., Akazawa, K., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.35 · Cited by 65
Long-term effects of amyloid, hypometabolism, and atrophy on neuropsychological functions
Ossenkoppele, R., van der Flier, W. M., Verfaillie, S. C. J., Vrenken, H., Versteeg, A., van Schijndel, R. A., Sikkes, S. A. M., Twisk, J. W. R., Adriaanse, S. M., Zwan, M. D., et al. (2014) · Neurology · doi:10.1212/wnl.0000000000000432 · Cited by 63
“The present results contradict the general view that amyloid pathology is only modestly correlated with cognition in AD dementia.(7,10,11,18,36) The majority of studies, however, only assessed cross-sectional cognitive data and these are congruent with the present cross-sectional results.”
ResultCongdon, E. E., Lin, Y., Rajamohamedsait, H. B., Shamir, D. B., Krishnaswamy, S., Rajamohamedsait, W. J., Rasool, S., González‐Calle, V., Levenga, J., Gu, J., et al. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0126-z · Cited by 64
“The hope is that this approach may be more effective than targeting Aβ in the later stages of the disease as tau pathology correlates better with dementia than Aβ plaques [8].”
BackgroundDal‐Pan, A., Dudonné, S., Bourassa, P., Bourdoulous, M., Tremblay, C., Desjardins, Y., & Calon, F. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160281 · Cited by 67
“Although the accumulation of plaques and tangles correlate to some extent with symptoms [5, 6], the exact neuropathological substrate of cognitive impairment in AD remains poorly defined.”
BackgroundProteopathic Strains and the Heterogeneity of Neurodegenerative Diseases
Walker, L. C. (2016) · Annual Review of Genetics · doi:10.1146/annurev-genet-120215-034943 · Cited by 60
“Genetic variations are estimated to contribute as risk factors in ~70–80% of all AD cases (95; 139; 155).”
BackgroundTau and atrophy: domain-specific relationships with cognition
Initiative, A. D. N., Digma, L. A., Madsen, J. R., Reas, E. T., Dale, A. M., Brewer, J. B., & Banks, S. J. (2019) · Alzheimer s Research & Therapy · doi:10.1186/s13195-019-0518-8 · Cited by 66
“While the associations with tau have been determined through studies of post-mortem brain tissue [9], we are now able to study them in vivo using PET ligands [10, 11].”
BackgroundGroot, C., Smith, R. A., Collij, L. E., Mastenbroek, S. E., Stomrud, E., Binette, A. P., Leuzy, A., Palmqvist, S., Mattsson, N., Strandberg, O. T., et al. (2024) · JAMA Neurology · doi:10.1001/jamaneurol.2024.1612 · Cited by 70
Intracellular and Extracellular Roles for Tau in Neurodegenerative Disease
Hanger, D. P., Lau, D. H. W., Phillips, E. C., Bondulich, M. K., Guo, T., Woodward, B. W., Pooler, A. M., & Noble, W. J. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132054 · Cited by 66
“241 In AD, the apparent stereotypic spread of tau pathol242 ogy from its initiation point, through the hippocampal 243 formation and into the limbic and association cortices, 244 mirrors the pattern of the cognitive deficits that are 245 observed clinically [70].”
Neuroglobin involvement in respiratory chain function and retinal ganglion cell integrity
Lechauve, C., Augustin, S., Cwerman‐Thibault, H., Bouaita, A., Forster, V., Célier, C., Rustin, P., Marden, M. C., Sahel, J., & Corral‐Debrinski, M. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.09.009 · Cited by 63
“It is well known that neurofibrillary tangle (aggregates of hyperphosphorylated tau) is highly correlated with the degree of dementia in AD patients [5].”
BackgroundBos, I., Verhey, F. R. J., Ramakers, I. H. G. B., Jacobs, H. I. L., Soininen, H. S., Freund‐Levi, Y., Hampel, H. J., Tsolaki, M., Wallin, Å. K., van Buchem, M. A., et al. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0328-9 · Cited by 62
“That elevated t-tau levels in the groups with one or both pathologies were found only in subjects with MCI is in line with previous work that strongly related tau to cognitive dysfunction [41].”
ResultSleep–wake regulation and the hallmarks of the pathogenesis of Alzheimer’s disease
Egroo, M. V., Narbutas, J., Chylinski, D., González, P. V., Maquet, P., Salmon, É., Bastin, C., Collette, F., & Vandewalle, G. (2019) · SLEEP · doi:10.1093/sleep/zsz017 · Cited by 66
“In the course of several neurodegenerative diseases, including AD, tau undergoes abnormal hyperphosphorylation, oligomerization, and then conversion into insoluble filamentous state [87, 88].”
BackgroundTau pathology in cognitively normal older adults
Ziontz, J., Bilgel, M., Shafer, A. T., Moghekar, A., Elkins, W., Helphrey, J. H., Gómez, G., June, D., McDonald, M. A., Dannals, R. F., et al. (2019) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1016/j.dadm.2019.07.007 · Cited by 67
“to the formation of neurofibrillary tangles, which are observed at autopsy in brains of almost all individuals older than 70 years [2].”
BackgroundDaulatzai, M. A. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1404-6 · Cited by 63
“Further, the abovementioned could be concurrent to other early hallmark pathologies of AD viz. tau accumulation in the ERC (Nelson et al. 2012), in the background of aging.”
Towards clinical application of tau PET tracers for diagnosing dementia due to Alzheimer's disease
Ossenkoppele, R., & Hansson, O. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12356 · Cited by 62
Ferrer, I., Andrés‐Benito, P., Ausín, K., Pamplona, R., del Río, J. A., Fernández‐Irigoyen, J., & Santamaría, E. (2021) · Brain Pathology · doi:10.1111/bpa.12996 · Cited by 61
“Most individuals with NFT pathology restricted to the transentorhinal and entorhinal cortices and part of the hippocampus (first stages: stages I– II) are cognitively normal; cases at middle stages (stages III– IV), in which there is the involvement of the hippocampus and limbic system, may not suffer any apparent cog…”
BackgroundUemura, M. T., Robinson, J. L., Cousins, K. A. Q., Tropea, T. F., Kargilis, D., McBride, J. D., Suh, E. R., Xie, S. X., Xu, Y., Porta, S., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02383-3 · Cited by 59
“Although neocortical LBs are highly significant correlates of cognitive impairment in LBD [33, 49], LATE( +) cases had lower MMSE scores than LATE(-) cases in LBD after controlling for LBD subtype and ADNC.”
BackgroundSelf-citationQiu, Y., Shen, X., Ravid, O., Atrakchi, D., Rand, D., Wight, A. E., Kim, H.-J., Zaltsman, S. L., Cooper, I., Beeri, M. S., et al. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2218915120 · Cited by 62
“Neuritic dystrophy, a central element of 5XFAD disease pathology consisting of swollen, bulbous-shaped neurites comprised of dysfunctional axons and terminals expressing the amyloid precursor protein (APP) (19), correlates with the clinical severity of dementia (20, 21).”
Cortical thinning of parahippocampal subregions in very early Alzheimer's disease
Krumm, S., Kivisaari, S. L., Probst, A., Monsch, A. U., Reinhardt, J., Ulmer, S., Stippich, C., Kressig, R. W., & Taylor, K. I. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.11.001 · Cited by 67
Cerami, C., Dubois, B., Boccardi, M., Monsch, A. U., Démonet, J., & Cappa, S. F. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.03.034 · Cited by 64
Arnsten, A. F. T., Datta, D., & Preuss, T. M. (2021) · American Journal of Primatology · doi:10.1002/ajp.23254 · Cited by 66
“Cognitive deficits correlate with NFTs, but not amyloid plaques (Nelson et al., 2012) suggesting that it is particularly important that we learn how tau phosphorylation arises in the aging association cortex.”
BackgroundElbatrawy, A. A., Hyeon, S. J., Yue, N., Osman, E. E. A., Choi, S. H., Lim, S., Kim, Y. K., Ryu, H., Cui, M., & Nam, G. (2021) · ACS Sensors · doi:10.1021/acssensors.1c00338 · Cited by 61
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“The pathological hallmarks of AD are the extracellular accumulations of amyloid-b (Ab) as plaques and as cerebral amyloid angiopathy (CAA), as well as intracellular neurofibrillary tangles (NFTs) (Nelson et al. 2012).”
BackgroundSelf-citation
Metadata
- Authors
- Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., Duyckaerts, C., Frosch, M. P., Haroutunian, V., Hof, P. R., Hulette, C. M., Hyman, B. T., Iwatsubo, T., Jellinger, K. A., Jicha, G. A., Kövari, E., Kukull, W. A., Leverenz, J. B., Love, S., Mackenzie, I. R., Mann, D. M., Masliah, E., McKee, A. C., Montine, T. J., Morris, J. C., Schneider, J. A., Sonnen, J. A., Thal, D. R., Trojanowski, J. Q., Troncoso, J. C., Wisniewski, T., Woltjer, R. L., & Beach, T. G.
- Affiliations
- University of Kentucky (US)
- Uppsala University (SE)
- Northwestern University (US)
- University of Geneva (CH)
- University of Maryland, Baltimore (US)
- University of British Columbia (CA)
- Albert Einstein College of Medicine (US)
- Harvard University (US)
- Boston University (US)
- Rush University Medical Center (US)
- Corresponding author
- Nelson, Peter T.
- ORCID
- Nelson, Peter T.
- Alafuzoff, Irina
- Bigio, Eileen H.
- Braak, Heiko
- Castellani, Rudolph J.
- Davies, Peter
- Tredici, Kelly Del
- Duyckaerts, Charles
- Frosch, Matthew P.
- Haroutunian, Vahram
- Hof, Patrick R.
- Hyman, Bradley T.
- Iwatsubo, Takeshi
- Jellinger, Kurt A.
- Jicha, Gregory A.
- Kukull, Walter A.
- Leverenz, James B.
- Love, Seth
- Mackenzie, Ian R.
- Mann, David M.
- Masliah, Eliezer
- McKee, Ann C.
- Montine, Thomas J.
- Morris, John C.
- Schneider, Julie A.
- Sonnen, Joshua A.
- Thal, Dietmar R.
- Trojanowski, John Q.
- Troncoso, Juan C.
- Woltjer, Randall L.
- Beach, Thomas G.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05
- Volume
- 71
- Issue
- 5
- Pages
- 362-381
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3560290
- OpenAlex
- W2074274706
- Semantic Scholar
- bce678baa6d56ad7c06197507d7903b6c7619507
- Cited by
- 2,050
- References
- 369
- Citations by year
- 2026: 115 · 2025: 153 · 2024: 166 · 2023: 161 · 2022: 213 · 2021: 205 · 2020: 194 · 2019: 179 · 2018: 139 · 2017: 134 · 2016: 108 · 2015: 95 · 2014: 98 · 2013: 72 · 2012: 17
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association
- Alzheimer Forschung Initiative
- Alzheimer's Society
- Deutsche Forschungsgemeinschaft
- Medical Research Council
- National Institute on Aging (AG-028383, AG 016976, AG-15819, AG13854, AG 10161, R01AG035071, AG-02219, AG 05136, P30AG028383, AG008017, U01AG006781, AG 05138, U01AG016976, P50AG005138, AG-06647, AG035071, P30AG010124, AG 05681, R01AG015819, P30AG008017, AG-10124, P30AG010161, R37AG022102, R01AG006647, P30AG008051, AG 08051, P50AG005681, R01AG022102, P50AG005136, P30AG013854, U19AG010483, R37AG006647, R01AG020245, P01AG002219, RF1AG015819)
- National Institute of Neurological Disorders and Stroke (R01NS073502)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, clinicopathological correlation, cognitive impairment, amyloid plaques, neurofibrillary tangles, disease severity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Humans, Statistics as Topic, Amyloid beta-Peptides, Neurofibrillary Tangles, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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