The DOI matches its Crossref record; 359 of the 369 references it cites were found in a registry or an index; 6 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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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
94 Not checked yet · 37 Own interpretation · 21 No basis given · 9 Own method · 3 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
“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.
None of the sources cited for this claim have been checked yet.
In the paper
“Subsequent studies have established that the densities of NPs correlate with antemortem cognitive impairment better than the densities of diffuse AβPs (45, 98, 106, 154, 189, 261).”
§ 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
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. 53
- Probably not a substantial claim. 21
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.
None of the sources cited for this claim have been checked yet.
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
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.
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.
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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.
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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.
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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.
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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.
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Probably not a substantial claim. It may state two separate claims as one.
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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.
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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.
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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.
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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.
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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.
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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]
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BackgroundInfluentialSelf-citationAmyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
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MethodResult
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Sorted by citations
Items 201–300 of 1,010
Dage, J. L., Wennberg, A. M. V., Airey, D. C., Hagen, C. E., Knopman, D. S., Machulda, M. M., Roberts, R. O., Jack, C. R., Petersen, R. C., & Mielke, M. M. (2016) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.06.001 · Cited by 145
Basheer, N., Smolek, T., Hassan, I., Liu, F., Iqbal, K., Zilka, N., & Novak, P. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-02113-z · Cited by 159
“Remarkably, the density and stereotyped spatiotemporal distribution of this neuro fi brillary pathology consistently correlate with the degree of cognitive decline, memory impairment, and brain atrophy [8 – 13].”
BackgroundChallenges of multimorbidity of the aging brain: a critical update
Jellinger, K. A., & Attems, J. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-014-1288-x · Cited by 154
“…pathology (Price et al. 2009); but, in general, the density of isocortical tangles correlates best with the severity of cognitive impairment (Nelson et al. 2007, 2012), which, however, may or may not apply for the oldest-old age group (Dolan et al. 2010; Purohit et al. 2008; Sinka et al.…”
BackgroundSelf-citationVégh, M. J., Heldring, C. M., Kamphuis, W., Hijazi, S., Timmerman, A. J., Li, K. W., van Nierop, P., Mansvelder, H. D., Hol, E. M., Smit, A. B., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/s40478-014-0076-z · Cited by 174
“hippocampus, and the mechanisms underlying memory loss in AD remain unclear [4].”
BackgroundPassive immunotherapies targeting Aβ and tau in Alzheimer's disease
Plotkin, S. S., & Cashman, N. R. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105010 · Cited by 161
Kumar, S. T., Jagannath, S., François, C., Vanderstichele, H., Stoops, E., & Lashuel, H. A. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.105086 · Cited by 157
Novak, P., Schmidt, R., Kontsekova, E., Kovacech, B., Smolek, T., Katina, S., Fialova, L., Prcina, M., Parrak, V., Dal-Bianco, P., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0436-1 · Cited by 147
Biomarker-Based Prediction of Longitudinal Tau Positron Emission Tomography in Alzheimer Disease
Leuzy, A., Smith, R., Cullen, N. C., Strandberg, O., Vogel, J. W., Binette, A. P., Borroni, E., Janelidze, S., Ohlsson, T., Jögi, J., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2021.4654 · Cited by 149
Amyloid β oligomers (AβOs) in Alzheimer’s disease
Mroczko, B., Groblewska, M., Litman‐Zawadzka, A., Kornhuber, J., & Lewczuk, P. (2017) · Journal of Neural Transmission · doi:10.1007/s00702-017-1820-x · Cited by 150
Recent update on the heterogeneity of the Alzheimer’s disease spectrum
Jellinger, K. A. (2021) · Journal of Neural Transmission · doi:10.1007/s00702-021-02449-2 · Cited by 155
Self-citationKnezović, A., Barilar, J. O., Ćurlin, M., Hof, P. R., Šimić, G., Riederer, P. F., & Šalković‐Petrišić, M. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1394-4 · Cited by 149
Self-citationAlzheimer disease in African American individuals: increased incidence or not enough data?
Barnes, L. L. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-021-00589-3 · Cited by 142
Tau, amyloid, and hypometabolism in a patient with posterior cortical atrophy
Ossenkoppele, R., Schonhaut, D. R., Baker, S. L., O’Neil, J. P., Janabi, M., Ghosh, P. M., Santos‐Santos, M., Miller, Z., Bettcher, B. M., Gorno‐Tempini, M. L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24321 · Cited by 151
“Tau pathology is a likely candidate given its devastating effects on synaptic function,(7) the strong correlation between the spatial distribution of tau and clinical evolution of the disease,(20) and the close association between postmortem tau burden and cognitive performance during life.(8) Tau imaging with PET pro…”
BackgroundProfound degeneration of wake‐promoting neurons in Alzheimer's disease
Oh, J. Y., Eser, R. A., Ehrenberg, A. J., Morales, D. O., Petersen, C., Kudlacek, J., Dunlop, S. R., Theofilas, P., Resende, E. D. P. F., Cosme, C. G., et al. (2019) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2019.06.3916 · Cited by 156
“AD-tau shows a stronger association with neuronal loss and clinical outcomes [11].”
BackgroundSelective suppression of the α isoform of p38 MAPK rescues late-stage tau pathology
Maphis, N., Jiang, S., Xu, G., Kokiko-Cochran, O. N., Roy, S. M., Van Eldik, L. J., Watterson, D. M., Lamb, B. T., & Bhaskar, K. (2016) · Alzheimer's Research & Therapy · doi:10.1186/s13195-016-0221-y · Cited by 147
“Recent studies suggest that NFT pathology closely correlates with neurodegeneration and cognitive decline [1, 2].”
Braak, H., Zetterberg, H., Tredici, K. D., & Blennow, K. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1139-0 · Cited by 148
Self-citationAlzheimer's disease: the amyloid hypothesis and the Inverse Warburg effect
Demetrius, L., Magistretti, P. J., & Pellerin, L. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2014.00522 · Cited by 151
Multi-Target Directed Donepezil-Like Ligands for Alzheimer's Disease
Unzeta, M., Esteban, G., Bolea, I., Fogel, W. A., Ramsay, R. R., Youdim, M. B. H., Tipton, K. F., & Marco, J. L. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00205 · Cited by 154
“In addition, direct Aβ-peptide neurotoxicity has been difficult to be identified in animal models, suggesting the existence of key intermediates between amyloidosis and neurodegeneration (Nelson et al., 2012; Serrano-Pozo et al., 2013).”
BackgroundResultThe Amygdala as a Locus of Pathologic Misfolding in Neurodegenerative Diseases
Nelson, P. T., Abner, E. L., Patel, E., Anderson, S., Wilcock, D. M., Kryscio, R. J., Eldik, L. J. V., Jicha, G. A., Gal, Z. T., Nelson, R. S., et al. (2017) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlx099 · Cited by 141
Self-citationChronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading
Jain, N., Lewis, C. A., Ulrich, J. D., & Holtzman, D. M. (2023) · Journal of Experimental Medicine · doi:10.1084/jem.20220654 · Cited by 146
“An important subtype of Aβ plaques includes neuritic plaques (NPs), which are defined as plaques surrounded with swollen, dystrophic neural processes also containing aggregated p-tau (Holtzman et al., 2011; Nelson et al., 2012).”
BackgroundA unifying hypothesis for Alzheimer's disease: from plaques to neurodegeneration
Edwards, F. A. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.03.003 · Cited by 140
“Tangles build up later than 397 plaques [64] and, together with synaptic loss, are more closely correlated with cognitive 398 decline [76].”
BackgroundThe aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Paspalas, C. D., Carlyle, B. C., Leslie, S., Preuss, T. M., Crimins, J. L., Huttner, A. J., van Dyck, C. H., Rosene, D. L., Nairn, A. C., & Arnsten, A. F. T. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2017.11.005 · Cited by 140
“NFTs accumulate within degenerating neurons and correlate with cognitive deficits [4,5].”
BackgroundResultInfluentialSelenica, M. B., Benner, L., Housley, S. B., Manchec, B., Lee, D. C., Nash, K. R., Kalin, J. H., Bergman, J. A., Kozikowski, A. P., Gordon, M. N., et al. (2014) · Alzheimer s Research & Therapy · doi:10.1186/alzrt241 · Cited by 148
“Given the positive correlation of tau pathology with cognitive impairment in AD patients [3], we examined how HDAC6 inhibition in vivo correlates with behavior and pathophysiological changes measured in treated rTg4510 mice (Figure 5J and Additional file 1).”
BackgroundFluorodeoxyglucose metabolism associated with tau‐amyloid interaction predicts memory decline
Hanseeuw, B. J., Betensky, R. A., Schultz, A. P., Papp, K. V., Mormino, E. C., Sepulcre, J., Bark, J. S., Cosio, D. M., LaPoint, M., Chhatwal, J. P., et al. (2017) · Annals of Neurology · doi:10.1002/ana.24910 · Cited by 140
“Alzheimer’s disease (AD) is a neurodegenerative disorder expressed clinically by a progressive memory decline leading to dementia in which brain amyloid-beta (Ab) plaques and tau neurofibrillary tangles slowly accumulate as the cardinal pathologic features.(1,2) Autopsy studies suggest that tau pathology appears in th…”
BackgroundElia, C. A., Tamborini, M., Rasile, M., Desiato, G., Marchetti, S., Swuec, P., Mazzitelli, S., Clemente, F., Anselmo, A., Matteoli, M., et al. (2019) · Cells · doi:10.3390/cells8091059 · Cited by 146
“We are aware that the correlation between plaque load and cognitive scores in humans has recently been questioned [59,60], prompting the scientific community to look for additional factors, beyond the “Amyloid Hypothesis”, as the etiological mechanism of AD.”
BackgroundAtherosclerosis and Alzheimer - diseases with a common cause? Inflammation, oxysterols, vasculature
Lathe, R., Tsitrina, A. A., & Kotelevtsev, Y. V. (2014) · BMC Geriatrics · doi:10.1186/1471-2318-14-36 · Cited by 141
“Aβ does not correlate precisely with clinical diagnosis of AD (reviewed in [352]), and the failure of Aβ immunotherapy to ameliorate AD pathology in clinical trials (not reviewed here) suggests that Aβ is not central, and is instead subservient to CH25H.”
BackgroundCeccom, J., Loukh, N., Lauwers‐Cancès, V., Touriol, C., Nicaise, Y., Gentil, C., Uro‐Coste, E., Pitson, S. M., Maurage, C., Duyckaerts, C. J., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-12 · Cited by 140
“These lesions are likely implicated in neuronal death and synaptic dysfunction associated with cerebral atrophy and cognitive impairment, characteristics of AD [2].”
BackgroundSelf-citationCanine Cognitive Dysfunction and Alzheimer’s Disease – Two Facets of the Same Disease?
Mihevc, S. P., & Majdič, G. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00604 · Cited by 152
“The Neuropathology in the Brain Parenchyma The most prominent neuropathological signs of AD are accumulation of Aβ in a form of extracellular plaques in the brain parenchyma and also in the walls of blood vessels (cerebral amyloid angiopathy, CAA), and abnormally phosphorylated protein TAU that accumulates in NFTs (Br…”
BackgroundBuchholz, S., & Zempel, H. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.13784 · Cited by 154
Multi-method investigation of factors influencing amyloid onset and impairment in three cohorts
Betthauser, T. J., Bilgel, M., Koscik, R. L., Jedynak, B., An, Y., Kellett, K. A., Moghekar, A., Jonaitis, E. M., Stone, C. K., Engelman, C. D., et al. (2022) · Brain · doi:10.1093/brain/awac213 · Cited by 133
Roberts, M., Sevastou, I., Imaizumi, Y., Mistry, K., Talma, S., Dey, M., Gartlon, J., Ochiai, H., Zhou, Z., Akasofu, S., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-0884-2 · Cited by 135
Da, X., Toledo, J. B., Zee, J., Wolk, D. A., Xie, S. X., Ou, Y., Shacklett, A., Parmpi, P., Shaw, L. M. J., Trojanowski, J. Q., et al. (2013) · NeuroImage Clinical · doi:10.1016/j.nicl.2013.11.010 · Cited by 144
“10% or more of the cases with a clinical diagnosis of AD do not have an underlying AD when assessed in neuropathological studies (Nelson et al., 2012; Toledo et al., 2012) and this percentage increases in the MCI stage.”
BackgroundSelf-citationMicroglial Malfunction: The Third Rail in the Development of Alzheimer's Disease
Mhatre, S. D., Tsai, C. A., Rubin, A. J., James, M. L., & Andreasson, K. I. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2015.08.006 · Cited by 134
“At these advanced stages, tau pathology is always found in association with ‘neuritic’ amyloid plaques that contain neurofibrillary tangles (NFTs) composed of aggregated hyperphosphorylated tau [5].”
New Insights Into Drug Discovery Targeting Tau Protein
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Tau PET Imaging in Neurodegenerative Disorders
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“It is to be emphasized that the impairment of cognitive domains on which the clinical diagnosis of AD is based is in most cases but not always correlate well with the extent of post-mortem AD neuropathology [26, 27].”
BackgroundTherapeutic strategies for tau mediated neurodegeneration
Yoshiyama, Y., Lee, V. M. ‐., & Trojanowski, J. Q. (2012) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp-2012-303144 · Cited by 137
Self-citationMicroglia-Mediated Neuroprotection, TREM2, and Alzheimer’s Disease: Evidence From Optical Imaging
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“However, there is a relatively weak correlation between plaque load and cognitive scores (12,13), suggesting that additional factors contribute to modulating neural injury caused by amyloid deposits.”
Ossenkoppele, R., Reimand, J., Smith, R. A., Leuzy, A., Strandberg, O. T., Palmqvist, S., Stomrud, E., Zetterberg, H., Initiative, T. A. D. N., Scheltens, P., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202114398 · Cited by 130
“…of tau pathology, Busche & Hyman, 2020), the phosphorylation, release and aggregation of tau proteins are tightly linked to the clinical and biological progression of AD (Savva et al, 2009; Nelson et al, 2012; Jack & Holtzman, 2013; Spires-Jones & Hyman, 2014; Mattsson-Carlgren et al, 2020a).”
BackgroundCerebral amyloid PET imaging in Alzheimer’s disease
Jack, C. R., Barrio, J. R., & Kepe, V. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1185-7 · Cited by 137
“[81] the authors concluded that “it is extraordinarily rare for a case with widespread, dense AD-type neocortical lesions to lack documented ante mortem cognitive decline”.”
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Neuroinflammatory Signals in Alzheimer Disease and APP/PS1 Transgenic Mice
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Amyloid-β pathology enhances pathological fibrillary tau seeding induced by Alzheimer PHF in vivo
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Blood-brain barrier leakage in Alzheimer’s disease: From discovery to clinical relevance
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Propagation of tau pathology in Alzheimer’s disease: identification of novel therapeutic targets
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“Progression of NFT pathology throughout the brain correlates well with decline in cognitive function [5].”
BackgroundSelf-citationIaccarino, L., Joie, R. L., Lesman‐Segev, O. H., Lee, E. Y., Hanna, L., Allen, I. E., Hillner, B. E., Siegel, B. A., Whitmer, R. A., Carrillo, M. C., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.3962 · Cited by 125
The role of amyloid oligomers in neurodegenerative pathologies
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Predicting future rates of tau accumulation on PET
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“, 2019; Long and Holtzman, 2019) is abundant evidence suggesting that tau (rather than amyloid-b) is the proteinopathy more closely associated with cognitive impairment among individuals in the Alzheimer’s continuum (Arriagada et al., 1992; Gomez-Isla et al., 1997; Bennett et al., 2004; Nelson et al., 2012; Brier et a…”
BackgroundSmall-molecule PET Tracers for Imaging Proteinopathies
Mathis, C. A., Lopresti, B. J., Ikonomović, M. D., & Klunk, W. E. (2017) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2017.06.003 · Cited by 124
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Microglial priming in Alzheimer’s disease
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“In all these advanced stages, it has been discovered that tau pathology is always accompanied with ‘neuritic’ amyloid plaques combined with NFTs that are composed of aggregated hyperphosphorylated tau (77).”
BackgroundThe amyloid cascade and Alzheimer's disease therapeutics: theory versus observation
Castellani, R. J., Plascencia‐Villa, G., & Perry, G. L. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0231-z · Cited by 130
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“A concern often raised against the importance of Aβ, is the fact that Aβ plaques show only a low-to-moderate correlation with cognitive decline (reviewed in (Nelson et al., 2012)).”
Systems-based proteomics to resolve the biology of Alzheimer’s disease beyond amyloid and tau
Rayaprolu, S., Higginbotham, L., Bagchi, P., Watson, C. M., Zhang, T., Levey, A. I., Rangaraju, S., & Seyfried, N. T. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-00840-3 · Cited by 118
APP/Aβ structural diversity and Alzheimer's disease pathogenesis
Roher, A. E., Kokjohn, T. A., Clarke, S. G., Sierks, M. R., Maarouf, C. L., Serrano, G. E., Sabbagh, M., & Beach, T. G. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.08.007 · Cited by 126
Self-citationMormino, E. C., & Papp, K. V. (2018) · Journal of Alzheimer s Disease · doi:10.3233/jad-179928 · Cited by 124
“When considering the postmortem literature, there are three consistent observations regarding the overall involvement of NFTs and Aβ plaques with respect to age and clinical status: (1) NFTs in early Braak regions are common in middle age and ubiquitous in older age (50% of 50 year olds and 90% of 70 years old have NF…”
DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases
Kousparou, C. A., Fyrilla, M., Stephanou, A., & Patrikios, I. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241310717 · Cited by 134
“The mainstay of diagnosis focuses on clinical assessment and more specifically on the clinical interview and cognitive testing [93].”
BackgroundConsensus Paper: Cerebellum and Ageing
Arleo, A., Bareš, M., Bernard, J. A., Bogoian, H. R., Bruchhage, M. M. K., Bryant, P., Carlson, E. S., Chan, C. C. H., Chen, L., Chung, C., et al. (2023) · The Cerebellum · doi:10.1007/s12311-023-01577-7 · Cited by 129
“The view that the cerebellum was largely spared the neuropathologic hallmarks of AD arose because cerebellar deposition of beta-amyloid plaques and neurofibrillary tangles were detected only in late-stage disease [131, 132].”
Is synaptic loss a unique hallmark of Alzheimer’s disease?
Scheff, S. W., Neltner, J. H., & Nelson, P. T. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2013.12.028 · Cited by 118
“However, even in extreme old age, the presence of many neocortical NFTs (Braak neurofibrillary stage VI) correlates with antemortem cognitive decline [48–50].”
BackgroundInfluentialSelf-citationCórdova‐Palomera, A., Kaufmann, T., Persson, K., Alnæs, D., Doan, N. T., Moberget, T., Lund, M. J., Barca, M. L., Engvig, A., Brækhus, A., et al. (2017) · Scientific Reports · doi:10.1038/srep40268 · Cited by 116
Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases
Salman, M. M., Al-Obaidi, Z. M. J., Kitchen, P., Loreto, A., Bill, R. M., & Wade‐Martins, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094688 · Cited by 121
“Although amyloid deposits are thought to develop before NFTs, amyloid burden is poorly correlated with disease progression, whereas NFT burden is more strongly correlated [70].”
BackgroundCross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults
Lowe, V. J., Bruinsma, T. J., Wiste, H. J., Min, H.-K., Weigand, S. D., Fang, P., Senjem, M. L., Therneau, T. M., Boeve, B. F., Josephs, K. A., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000007728 · Cited by 107
Synaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01246-y · Cited by 128
FDG-PET in tau-negative amnestic dementia resembles that of autopsy-proven hippocampal sclerosis
Botha, H., Mantyh, W. G., Murray, M. E., Knopman, D. S., Przybelski, S. A., Wiste, H. J., Graff‐Radford, J., Josephs, K. A., Schwarz, C. G., Kremers, W. K., et al. (2018) · Brain · doi:10.1093/brain/awy049 · Cited by 112
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“The occurrence of neuronal death generally parallels NFT formation, and the clinical features and severity of AD better correlate with NFT pathology than Aβ deposition [18].”
BackgroundSynaptic Dysfunction in Alzheimer’s Disease: Aβ, Tau, and Epigenetic Alterations
Li, K., Wei, Q., Liu, F., Hu, F., Xie, A., Zhu, L., & Liu, D. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0533-3 · Cited by 121
Tau Accumulation in Clinically Normal Older Adults Is Associated with Hippocampal Hyperactivity
Huijbers, W., Schultz, A. P., Papp, K. V., LaPoint, M. R., Hanseeuw, B. J., Chhatwal, J. P., Hedden, T., Johnson, K. A., & Sperling, R. A. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1397-18.2018 · Cited by 118
“Histopathological studies indicate tau aggregation starts in the entorhinal cortex (Braak and Braak, 1991; Nelson et al., 2012) and is nearly ubiquitous in advanced aging, whereas tau in the inferior temporal cortex is indicative of more advanced stages of preclinical AD (Jack et al., 2016).”
BackgroundMonteiro, C., Tóth, B. I., Brunstein, F., Bobbala, A., Datta, S., Ceniceros, R., Bohorquez, S. M. S., Anania, V. G., Wildsmith, K. R., Schauer, S. P., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207663 · Cited by 113
Kazim, S. F., & Iqbal, K. (2016) · Molecular Neurodegeneration · doi:10.1186/s13024-016-0119-y · Cited by 126
“The NFT load in AD brain are known to correlate better with cognitive decline [58].”
BackgroundLocus coeruleus at asymptomatic early and middle Braak stages of neurofibrillary tangle pathology
Andrés‐Benito, P., Fernández‐Dueñas, V., Carmona, M., Escobar, L. A., Torrejón-Escribano, B., Aso, E., Ciruela, F., & Ferrer, I. (2017) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12386 · Cited by 114
Deregulation of neuronal miRNAs induced by amyloid-β or TAU pathology
Sierksma, A., Lu, A., Salta, E., Vanden Eynden, E., Callaerts-Vegh, Z., D’Hooge, R., Blum, D., Buée, L., Fiers, M., & De Strooper, B. (2018) · Molecular Neurodegeneration · doi:10.1186/s13024-018-0285-1 · Cited by 120
Kontsekova, E., Zilka, N., Kovacech, B., Skrabana, R., & Novak, M. (2014) · Alzheimer's Research & Therapy · doi:10.1186/alzrt277 · Cited by 112
“It has been shown that diseased modified tau proteins play an essential role in the clinical manifestation of AD [7,9,56].”
BackgroundEdwards, A. L., Collins, J. A., Junge, C., Kordasiewicz, H., Mignon, L., Wu, S., Li, Y., Lin, L., DuBois, J., Hutchison, R. M., et al. (2023) · JAMA Neurology · doi:10.1001/jamaneurol.2023.3861 · Cited by 113
The informed road map to prevention of Alzheimer Disease: a call to arms
McDade, E., Llibre-Guerra, J. J., Holtzman, D. M., Morris, J. C., & Bateman, R. J. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00467-y · Cited by 89
“Tau pathology in the brain correlates much more highly with clinical status and dementia than do amyloid plaques, atrophy, or perturbations of glucose metabolism [55, 56].”
BackgroundSelf-citationMotor function deficits in the 12 month-old female 5xFAD mouse model of Alzheimer’s disease
O’Leary, T. P., Robertson, A., Chipman, P., Rafuse, V. F., & Brown, R. E. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.09.009 · Cited by 110
Novák, P., Žilka, N., Žilková, M., Kováčech, B., Škrabana, R., Ondrus, M., Fialová, L., Kontseková, E., Otto, M., & Novák, M. (2019) · The Journal of Prevention of Alzheimer s Disease · doi:10.14283/jpad.2018.45 · Cited by 115
“Long neglected by a large portion of the AD field and seen as a by-product of amyloid β pathology, neurofibrillary tau pathology has been established as the closest correlate of cortical atrophy (5) and clinical progression in AD (6-8).”
Xia, Y., Prokop, S., Gorion, K.-M. M., Kim, J. D., Sorrentino, Z. A., Bell, B. M., Manaois, A. N., Chakrabarty, P., Davies, P., & Giasson, B. I. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00967-w · Cited by 118
“However as the density of tau inclusions strongly correlates with cognitive decline [63], the “tau hypothesis” proposes that pathogenic tau is the main toxic factor that drives neurodegeneration in AD and other related diseases [43].”
Self-citationWard, A. M., Mormino, E. C., Huijbers, W., Schultz, A. P., Hedden, T., & Sperling, R. A. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.06.028 · Cited by 117
Is amyloid-β harmful to the brain? Insights from human imaging studies
Jagust, W. (2016) · Brain · doi:10.1093/brain/awv326 · Cited by 110
“constituent of the neurofibrillary tangle that is more closely related to cognitive outcomes than is the amyloid-b plaque (Nelson et al., 2012).”
BackgroundChiotis, K., Saint‐Aubert, L., Rodriguez‐Vieitez, E., Leuzy, A., Almkvist, O., Savitcheva, I., Jonasson, M., Lubberink, M., Wall, A., Antoni, G., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.108 · Cited by 112
[F-18]-AV-1451 binding correlates with postmortem neurofibrillary tangle Braak staging
Marquié, M., Siao Tick Chong, M., Antón-Fernández, A., Verwer, E. E., Sáez-Calveras, N., Meltzer, A. C., Ramanan, P., Amaral, A. C., Gonzalez, J., Normandin, M. D., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1740-8 · Cited by 109
“Neurofibrillary pathology (neurofibrillary tangles (NFTs) and neuropil threads) in AD brains follows a * Teresa Gómez-Isla tgomezisla@partners.org 1 MassGeneral Institute for NeuroDegenerative Disease, Charlestown, MA, USA 2 Department of Neurology, Massachusetts General Hospital, WACC Suite 715., 15th Parkman St., Bo…”
InfluentialSelf-citationTau biology, tauopathy, traumatic brain injury, and diagnostic challenges
Castellani, R. J., & Perry, G. (2019) · Journal of Alzheimer’s Disease · doi:10.3233/jad-180721 · Cited by 110
Self-citationTemporal T807 binding correlates with CSF tau and phospho-tau in normal elderly
Chhatwal, J. P., Schultz, A. P., Marshall, G. A., Boot, B., Gomez-Isla, T., Dumurgier, J., LaPoint, M., Scherzer, C., Roe, A. D., Hyman, B. T., et al. (2016) · Neurology · doi:10.1212/wnl.0000000000003050 · Cited by 106
Self-citationVascular Risk and β ‐Amyloid Are Synergistically Associated with Cortical Tau
Rabin, J. S., Yang, H., Schultz, A. P., Hanseeuw, B. J., Hedden, T., Viswanathan, A., Gatchel, J. R., Marshall, G. A., Kilpatrick, E. P., Klein, H., et al. (2018) · Annals of Neurology · doi:10.1002/ana.25399 · Cited by 110
Tau deposition is associated with functional isolation of the hippocampus in aging
Harrison, T. M., Maaß, A., Adams, J. N., Du, R., Baker, S. L., & Jagust, W. J. (2019) · Nature Communications · doi:10.1038/s41467-019-12921-z · Cited by 113
Human neural stem cell-derived extracellular vesicles mitigate hallmarks of Alzheimer’s disease
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“63 These ambiguities suggest the vital need to expand the choice of AD biomarkers beyond A β and tau for better diagnosis and prognosis of AD.”
Baldeweg, T., & Hirsch, S. R. (2015) · International Journal of Psychophysiology · doi:10.1016/j.ijpsycho.2014.03.008 · Cited by 108
“This is in stark contrast to AD patients, who showed preservedMMN despite exhibiting more severe memory impairments, presumably caused by themedial temporal emphasis of Alzheimer's disease pathology (Braak and Braak, 1995; Nelson et al., 2012).”
ResultSerrano‐Pozo, A., Qian, J., Monsell, S. E., Frosch, M. P., Betensky, R. A., & Hyman, B. T. (2013) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0000000000000016 · Cited by 106
“The relationships between the neuropathologic findings at autopsy and their clinical correlates in AD have been a matter of extensive study and debate (12).”
BackgroundSelf-citationRepetitive negative thinking is associated with amyloid, tau, and cognitive decline
Marchant, N. L., Lovland, L. R., Jones, R., Binette, A. P., Gonneaud, J., Arenaza‐Urquijo, E. M., Chételat, G., & Villeneuve, S. (2020) · Alzheimer s & Dementia · doi:10.1002/alz.12116 · Cited by 115
Detectable Neuropsychological Differences in Early Preclinical Alzheimer’s Disease: A Meta-Analysis
Han, S. D., Nguyen, C. P., Stricker, N. H., & Nation, D. A. (2017) · Neuropsychology Review · doi:10.1007/s11065-017-9345-5 · Cited by 121
“Tau neuropathology has consistently shown associations with memory measures (Nelson et al. 2012), and memory measures have long been associated with clinically-relevant progression of AD.”
BackgroundCytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice
Babcock, A. A., Ilkjær, L., Clausen, B. H., Villadsen, B., Dissing-Olesen, L., Bendixen, A. T. M., Lyck, L., Lambertsen, K. L., & Finsen, B. (2015) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2015.03.006 · Cited by 107
“Ab plaque burden is nonetheless a relatively weak pathological correlate of cognitive decline in Alzheimer’s disease (Nelson et al., 2012).”
BackgroundExtracellular Vesicle Biology in Alzheimer’s Disease and Related Tauopathy
DeLeo, A. M., & Ikezu, T. (2017) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-017-9768-z · Cited by 109
“In either case, the deposition of NFTs is the best clinically correlated marker of AD progression (Nelson et al. 2012; Schöll et al. 2016).”
Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease
Fowler, S. L., Behr, T. S., Turkes, E., O'Brien, D. P., Cauhy, P. M., Rawlinson, I., Edmonds, M. J., Foiani, M. S., Schaler, A. W., Crowley, G., et al. (2024) · Nature Neuroscience · doi:10.1038/s41593-024-01801-5 · Cited by 123
Tau reduction in the presence of amyloid-β prevents tau pathology and neuronal death in vivo
DeVos, S. L., Corjuc, B. T., Commins, C., Dujardin, S., Bannon, R. N., Corjuc, D., Moore, B. D., Bennett, R. E., Jorfi, M., Gonzales, J. A., et al. (2018) · Brain · doi:10.1093/brain/awy117 · Cited by 106
Self-citationOndrejčák, T., Klyubin, I. V., Corbett, G. T., Fraser, G. M., Hong, W., Mably, A. J., Gardener, M. J., Hammersley, J., Perkinton, M. S., Billinton, A., et al. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1700-18.2018 · Cited by 110
“Indeed, tau pathology and glutamatergic synaptic loss correlate with the severity of dementia in AD (Terry et al., 1991; Terry, 2000; Nelson et al., 2009, 2012).”
Background
Metadata
- Authors
- Nelson, P. T., Alafuzoff, I., Bigio, E. H., Bouras, C., Braak, H., Cairns, N. J., Castellani, R. J., Crain, B. J., Davies, P., Tredici, K. D., Duyckaerts, C., Frosch, M. P., Haroutunian, V., Hof, P. R., Hulette, C. M., Hyman, B. T., Iwatsubo, T., Jellinger, K. A., Jicha, G. A., Kövari, E., Kukull, W. A., Leverenz, J. B., Love, S., Mackenzie, I. R., Mann, D. M., Masliah, E., McKee, A. C., Montine, T. J., Morris, J. C., Schneider, J. A., Sonnen, J. A., Thal, D. R., Trojanowski, J. Q., Troncoso, J. C., Wisniewski, T., Woltjer, R. L., & Beach, T. G.
- Affiliations
- University of Kentucky (US)
- Uppsala University (SE)
- Northwestern University (US)
- University of Geneva (CH)
- University of Maryland, Baltimore (US)
- University of British Columbia (CA)
- Albert Einstein College of Medicine (US)
- Harvard University (US)
- Boston University (US)
- Rush University Medical Center (US)
- Corresponding author
- Nelson, Peter T.
- ORCID
- Nelson, Peter T.
- Alafuzoff, Irina
- Bigio, Eileen H.
- Braak, Heiko
- Castellani, Rudolph J.
- Davies, Peter
- Tredici, Kelly Del
- Duyckaerts, Charles
- Frosch, Matthew P.
- Haroutunian, Vahram
- Hof, Patrick R.
- Hyman, Bradley T.
- Iwatsubo, Takeshi
- Jellinger, Kurt A.
- Jicha, Gregory A.
- Kukull, Walter A.
- Leverenz, James B.
- Love, Seth
- Mackenzie, Ian R.
- Mann, David M.
- Masliah, Eliezer
- McKee, Ann C.
- Montine, Thomas J.
- Morris, John C.
- Schneider, Julie A.
- Sonnen, Joshua A.
- Thal, Dietmar R.
- Trojanowski, John Q.
- Troncoso, Juan C.
- Woltjer, Randall L.
- Beach, Thomas G.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-05
- Volume
- 71
- Issue
- 5
- Pages
- 362-381
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC3560290
- OpenAlex
- W2074274706
- Semantic Scholar
- bce678baa6d56ad7c06197507d7903b6c7619507
- Cited by
- 2,050
- References
- 369
- Citations by year
- 2026: 115 · 2025: 153 · 2024: 166 · 2023: 161 · 2022: 213 · 2021: 205 · 2020: 194 · 2019: 179 · 2018: 139 · 2017: 134 · 2016: 108 · 2015: 95 · 2014: 98 · 2013: 72 · 2012: 17
- FWCI
- 12.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Alzheimer's Association
- Alzheimer Forschung Initiative
- Alzheimer's Society
- Deutsche Forschungsgemeinschaft
- Medical Research Council
- National Institute on Aging (AG-028383, AG 016976, AG-15819, AG13854, AG 10161, R01AG035071, AG-02219, AG 05136, P30AG028383, AG008017, U01AG006781, AG 05138, U01AG016976, P50AG005138, AG-06647, AG035071, P30AG010124, AG 05681, R01AG015819, P30AG008017, AG-10124, P30AG010161, R37AG022102, R01AG006647, P30AG008051, AG 08051, P50AG005681, R01AG022102, P50AG005136, P30AG013854, U19AG010483, R37AG006647, R01AG020245, P01AG002219, RF1AG015819)
- National Institute of Neurological Disorders and Stroke (R01NS073502)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, clinicopathological correlation, cognitive impairment, amyloid plaques, neurofibrillary tangles, disease severity
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cognition Disorders, Humans, Statistics as Topic, Amyloid beta-Peptides, Neurofibrillary Tangles, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-10, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-10 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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