National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approach
Open accessAbstract
We present a practical guide for the implementation of recently revised National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease (AD). Major revisions from previous consensus criteria are: (1) recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment, (2) an "ABC" score for AD neuropathologic change that incorporates histopathologic assessments of amyloid β deposits (A), staging of neurofibrillary tangles (B), and scoring of neuritic plaques (C), and (3) more detailed approaches for assessing commonly co-morbid conditions such as Lewy body disease, vascular brain injury, hippocampal sclerosis, and TAR DNA binding protein (TDP)-43 immunoreactive inclusions. Recommendations also are made for the minimum sampling of brain, preferred staining methods with acceptable alternatives, reporting of results, and clinico-pathologic correlations.
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27 of 65 cited sources checked · 12 supported · 0 flagged · accuracy not yet measured
- Premisecitation
AD neuropathologic changes may occur in the apparent absence of cognitive impairment.
“recognition that AD neuropathologic changes may occur in the apparent absence of cognitive impairment”
- Also stated in: § CLINICO-PATHOLOGIC CORRELATION · plain
“Similar neuropathologic changes, albeit usually at lower levels, also occur in individuals who did not show cognitive or behavioral impairments during life [54].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [54] Sperling RA, Aisen PS, Beckett LA et al (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292 source
- Also stated in: § CLINICO-PATHOLOGIC CORRELATION · plain
- Premisecitation
Greater sensitivity for detecting Lewy bodies can be achieved with immunohistochemistry for α-synuclein compared to H&E.
“LBs may be detected in neurons of medulla, pons and midbrain with hematoxylin and eosin (H&E)-stained sections; however, greater sensitivity can be achieved with immunohistochemistry for α-synuclein and this approach is strongly preferred [3,4,13].”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [3] Alafuzoff I, Parkkinen L, Al-Sarraj S et al (2008) Assessment of alpha-synuclein pathology: a study of the BrainNet Europe Consortium. J Neuropathol Exp Neurol 67:125–143 source
The Introduction (p. 125) says consensus guidelines recommend α-synuclein immunohistochemistry for synucleinopathies, supporting the preference for that approach. The paper’s staining results and Discussion assess variation among immunohistochemical methods, but do not establish that immunohistochemistry detects Lewy bodies more sensitively than H&E; searches for H&E and hematoxylin–eosin found no such comparison. (LLM, conf=0.84)
Experimental — accuracy not yet measured - cites [4] Alafuzoff I, Pikkarainen M, Al-Sarraj S et al (2006) Interlaboratory comparison of assessments of Alzheimer disease-related lesions: a study of the BrainNet Europe Consortium. J Neuropathol Exp Neurol 65:740–757 source
- cites [13] Beach TG, White CL, Hamilton RL et al (2008) Evaluation of alpha-synuclein immunohistochemical methods used by invited experts. Acta Neuropathol 116:277–288 source
The Introduction (page unavailable) calls α-synuclein immunohistochemistry the method of choice for diagnosing Lewy body disorders, supporting its preferred use. The paper compares immunohistochemical methods with one another, however, and does not establish that they detect Lewy bodies more sensitively than H&E staining. (LLM, conf=0.84)
Experimental — accuracy not yet measured
- Premisecitation
Multiple MVLs in standard sections of brain are associated with increased likelihood of cognitive impairment or dementia.
“one MVL identified in standard sections of brain (Table 1 regions shaded green) is of unclear relationship to cognitive function, while multiple MVLs in these regions are associated with increased likelihood of cognitive impairment or dementia [24,52,62].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [24] Gorelick PB, Scuteri A, Black SE et al (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:2672–2713 source
Section 3.2 (page not available in our copy) reports that some studies associate multiple microscopic infarcts with dementia, even after accounting for macroscopic infarcts. It does not establish the claim for MVLs generally or specify that the lesions were identified in standard brain sections. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [52] Sonnen JA, Larson EB, Crane PK et al (2007) Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 62:406–413 source
- cites [62] White L (2009) Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study. J Alzheimers Dis 18:713–725 source
- Premisecitation
AD neuropathologic change can predate onset of symptoms by years.
“Clinico-pathologic correlations for individuals without cognitive impairment should indicate that it is possible for AD neuropathologic change to predate onset of symptoms by years [54].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [54] Sperling RA, Aisen PS, Beckett LA et al (2011) Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:280–292 source
- Premisecitation
One MVL identified in standard sections of brain is of unclear relationship to cognitive function.
“one MVL identified in standard sections of brain (Table 1 regions shaded green) is of unclear relationship to cognitive function, while multiple MVLs in these regions are associated with increased likelihood of cognitive impairment or dementia [24,52,62].”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [24] Gorelick PB, Scuteri A, Black SE et al (2011) Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 42:2672–2713 source
Section 3.2 (page unavailable) says the number of infarcts needed for cognitive impairment is difficult to determine and reports that multiple microscopic infarcts may be related to dementia. It does not specifically assess the cognitive significance of one MVL identified in standard brain sections. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [52] Sonnen JA, Larson EB, Crane PK et al (2007) Pathological correlates of dementia in a longitudinal, population-based sample of aging. Ann Neurol 62:406–413 source
- cites [62] White L (2009) Brain lesions at autopsy in older Japanese-American men as related to cognitive impairment and dementia in the final years of life: a summary report from the Honolulu-Asia aging study. J Alzheimers Dis 18:713–725 source
- Interpretationcitation
LBD observed in individuals without apparent cognitive or motor deficit may represent pre-clinical LBD.
“this may represent pre-clinical LBD [12,22,31].”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [12] Beach TG, Adler CH, Sue LI et al (2008) Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol 115:445–451 source
- cites [22] Dickson DW, Fujishiro H, DelleDonne A et al (2008) Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease. Acta Neuropathol 115:437–444 source
- cites [31] Jicha GA, Schmitt FA, Abner E et al (2010) Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiol Aging 31:1805–1813 source
- Premisecitation
Lewy bodies are frequent in some early-onset familial AD cases.
“LBs are frequent in the setting of moderate-to-severe levels of AD neuropathologic change [27,59], including some early-onset familial AD cases [32,33].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [32] Leverenz JB, Fishel MA, Peskind ER et al (2006) Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. Arch Neurol 63:370–376 source
- cites [33] Lippa CF, Duda JE, Grossman M et al (2007) DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68:812–819 source
- Premisenone given
Accumulation of Aβ plaques and NFTs follows distinct regional progressions across brain regions as AD advances.
“Accumulation of Aβ plaques and NFTs follows distinct regional progressions across brain regions as AD advances.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [14] Braak H, Alafuzoff I, Arzberger T et al (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol 112:389–404 source
The staging-system section describes a predictable regional progression of neurofibrillary pathology, from transentorhinal and entorhinal regions to limbic and then neocortical areas. It does not describe a separate regional progression of Aβ plaques or compare that progression with NFTs. Its references to neuritic plaques occur in the context of tau-immunoreactive pathology, not an Aβ-plaque staging scheme. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [15] Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239–259 source
- cites [57] Thal DR, Rub U, Orantes M, Braak H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58:1791–1800 source
- Premisecitation
Cerebrovascular disease and vascular brain injury commonly are encountered in the brains with AD neuropathologic change.
“CVD and vascular brain injury (VBI) [50] commonly are encountered in the brains with AD neuropathologic change [25].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [25] Grinberg LT, Thal DR (2010) Vascular pathology in the aged human brain. Acta Neuropathol 119:277–290 source
The ‘Cerebral amyloid angiopathy’ section (page unavailable) reports that around 80–100% of AD patients have CAA, supporting the claim that cerebrovascular disease commonly accompanies AD pathology. It identifies infarction and hemorrhage as possible complications of CAA, but does not establish that vascular brain injury itself is commonly found in AD brains. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Premisecitation
Lewy bodies are frequent in the setting of moderate-to-severe levels of AD neuropathologic change.
“LBs are frequent in the setting of moderate-to-severe levels of AD neuropathologic change [27,59], including some early-onset familial AD cases [32,33].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [27] Hamilton RL (2000) Lewy bodies in Alzheimer’s disease: a neuropathological review of 145 cases using alpha-synuclein immunohistochemistry. Brain Pathol 10:378–384 source
- cites [59] Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697 source
- Premisecitation
Higher levels of AD neuropathologic change are typically correlated with greater likelihood of cognitive impairment.
“For cases with incomplete clinical history, higher levels of AD neuropathologic change typically are correlated with greater likelihood of cognitive impairment [29].”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [29] Hyman BT, Phelps CH, Beach TG et al (2011) National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease. Alzheimer’s Dement (in press) source
- Premisecitation
Amygdala-predominant LBD typically occurs in the context of advanced AD neuropathologic change.
““Amygdala-predominant LBD” typically occurs in the context of advanced AD neuropathologic change [59].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [59] Uchikado H, Lin WL, DeLucia MW, Dickson DW (2006) Alzheimer disease with amygdala Lewy bodies: a distinct form of alpha-synucleinopathy. J Neuropathol Exp Neurol 65:685–697 source
- Premisecitation
LBD has been observed in individuals without apparent cognitive or motor deficit, though much less common than AD neuropathologic change.
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1,49]; this may represent pre-clinical LBD [12,22,31].”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [1] Adler CH, Connor DJ, Hentz JG et al (2010) Incidental Lewy body disease: clinical comparison to a control cohort. Mov Disord 25:642–646 source
The Abstract and Results describe autopsy-confirmed incidental Lewy body disease in people without diagnosed dementia or parkinsonism, with motor and cognitive findings largely comparable to controls. The paper does not establish that Lewy body disease is much less common than AD neuropathologic change; its AD count refers to excluded cases with an AD diagnosis, not the prevalence of neuropathologic change. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [49] Saito Y, Ruberu NN, Sawabe M et al (2004) Lewy body-related alpha-synucleinopathy in aging. J Neuropathol Exp Neurol 63:742–749 source
- Premisecitation
Neocortical LBD is correlated with greater likelihood of cognitive impairment.
“For cases with incomplete clinical history, we note that “Neocortical LBD” is correlated with greater likelihood of cognitive impairment [1,11-13,22,31-33,38,46,49,52].”
Quote in the paperNot a substantial claim8 of 10 sources checked- cites [1] Adler CH, Connor DJ, Hentz JG et al (2010) Incidental Lewy body disease: clinical comparison to a control cohort. Mov Disord 25:642–646 source
The Results report that none of the ILBD cases had neocortical Lewy body stage, so this cohort cannot establish whether neocortical LBD is associated with cognitive impairment. The Discussion says it is unclear whether cases at different stages would show different cognitive findings. I searched for a neocortical-stage comparison, but our copy does not report one. (LLM, conf=0.78)
Experimental — accuracy not yet measured - cites [11] Beach TG, Adler CH, Lue L et al (2009) Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol 117:613–634 source
- cites [12] Beach TG, Adler CH, Sue LI et al (2008) Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol 115:445–451 source
The Results and discussion (page unavailable) report that the studied cases were brainstem-predominant or limbic, with no neocortical cases. They also report no significant MMSE difference between the assessed incidental Lewy body disease cases and controls. The paper therefore does not address whether neocortical Lewy body disease is associated with a greater likelihood of cognitive impairment. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [13] Beach TG, White CL, Hamilton RL et al (2008) Evaluation of alpha-synuclein immunohistochemical methods used by invited experts. Acta Neuropathol 116:277–288 source
The Methods (Human subjects; page unavailable) say the selected cases had varying synuclein pathology and diagnoses, but the study used them to assess staining-method sensitivity. The Discussion (page unavailable) addresses detection and grading of pathology, not whether neocortical Lewy body disease correlates with cognitive impairment. Searches for neocortical disease, cognitive impairment, dementia, and clinical correlation found no passage establishing the claimed relationship. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [22] Dickson DW, Fujishiro H, DelleDonne A et al (2008) Evidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease. Acta Neuropathol 115:437–444 source
- cites [31] Jicha GA, Schmitt FA, Abner E et al (2010) Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease. Neurobiol Aging 31:1805–1813 source
The Results report cognitive decline in 9 of 15 cases with neocortical Lewy body disease, supporting a link between the pathology and impairment. But six cases had no charted cognitive decline, and the paper does not establish that neocortical LBD confers a greater likelihood of impairment than an appropriate comparison group. Page numbers are unavailable in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [32] Leverenz JB, Fishel MA, Peskind ER et al (2006) Lewy body pathology in familial Alzheimer disease: evidence for disease- and mutation-specific pathologic phenotype. Arch Neurol 63:370–376 source
The Results compare neocortical Lewy body pathology across familial Alzheimer disease mutations, not across levels of cognitive impairment. The Comment section says detailed clinical evaluations were often unavailable. Searches for cognitive impairment and dementia status found no analysis linking neocortical pathology to a greater likelihood of impairment. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [33] Lippa CF, Duda JE, Grossman M et al (2007) DLB and PDD boundary issues: diagnosis, treatment, molecular pathology, and biomarkers. Neurology 68:812–819 source
- cites [38] McKeith IG, Dickson DW, Lowe J et al (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65:1863–1872 source
The Pathology section lists diffuse neocortical Lewy-related pathology among the subtypes used to assess the likelihood of a typical DLB clinical syndrome. Table 1 says dementia, involving progressive cognitive decline, is essential to that syndrome. The copy does not specifically show that neocortical LBD is associated with a greater likelihood of cognitive impairment than other LBD subtypes. (LLM, conf=0.76)
Experimental — accuracy not yet measured - cites [46] Nelson PT, Kryscio RJ, Jicha GA et al (2009) Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies. Neurology 73:1127–1133 source
- Premisecitation
Relatively isolated HS may occur in very old individuals.
“Relatively isolated HS may occur in very old individuals, and in this context it is associated with TDP-43-immunoreactive inclusions and with cognitive impairment [45,47].”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [45] Nelson PT, Abner EL, Schmitt FA et al (2010) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 20:66–79 source
The Results describe an elderly autopsy cohort that included people over 80, and the Discussion reports hippocampal sclerosis (HS) in the cohort. However, our copy does not identify cases of relatively isolated HS or establish that those cases occurred specifically in very old individuals. (LLM, conf=0.78)
Experimental — accuracy not yet measured - cites [47] Nelson PT, Schmitt FA, Lin Y et al (2011) Hippocampal sclerosis in advanced age: clinical and pathological features. Brain 134:1506–1518 source
- Premisecitation
Immunohistochemical stains for neuritic processes identify specific, partially overlapping subtypes of dystrophic neurites that may differ in disease relevance.
“immunohistochemical stains for neuritic processes, such as amyloid precursor protein, ubiquitin, neurofilament or phospho-tau, will identify specific, and partially overlapping, subtypes of dystrophic neurites that may differ in disease relevance [21].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Dickson DW (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56:321–339 source
- Premisecitation
Cerebral amyloid angiopathy (CAA) is very commonly observed in cases with parenchymal Aβ plaques.
“Although cerebral amyloid angiopathy (CAA) is not considered in the “ABC” score, it is very commonly observed in cases with parenchymal Aβ plaques and should be evaluated and reported systematically as well as appreciated for its potential pathophysiological significance [56,61].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [56] Thal DR, Griffin WS, de Vos RA, Ghebremedhin E (2008) Cerebral amyloid angiopathy and its relationship to Alzheimer’s disease. Acta Neuropathol 115:599–609 source
- cites [61] Vonsattel JP, Myers RH, Hedley-Whyte ET et al (1991) Cerebral amyloid angiopathy without and with cerebral hemorrhages: a comparative histological study. Ann Neurol 30:637–649 source
- Premisecitation
Some forms of prion disease can overlap with AD.
“Finally, not only can the neuropathologic changes of prion disease be co-morbid with AD, but some forms of prion disease can overlap with AD and need to be distinguished with special stains [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Dlouhy SR, Hsiao K, Farlow MR et al (1992) Linkage of the Indiana kindred of Gerstmann-Straussler-Scheinker disease to the prion protein gene. Nat Genet 1:64–67 source
- Premisecitation
TDP-43 immunoreactive inclusions are commonly observed in cases with LBD.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [43] Nakashima-Yasuda H, Uryu K, Robinson J et al (2007) Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases. Acta Neuropathol 114:221–229 source
- Interpretationnone given
AD neuropathologic change is a continuum that underlies the progression of AD from preclinical to dementia stage.
“The new consensus criteria recognize the continuum of AD neuropathologic change that underlies the progression of this disease from preclinical to dementia stage.”
Quote in the paperSubstantial claim - Premisecitation
Prion disease neuropathologic changes can be co-morbid with AD.
“Finally, not only can the neuropathologic changes of prion disease be co-morbid with AD, but some forms of prion disease can overlap with AD and need to be distinguished with special stains [23].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [23] Dlouhy SR, Hsiao K, Farlow MR et al (1992) Linkage of the Indiana kindred of Gerstmann-Straussler-Scheinker disease to the prion protein gene. Nat Genet 1:64–67 source
- Premisecitation
TDP-43 immunoreactive inclusions are observed in about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [8] Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445 source
- cites [28] Hatanpaa KJ, Blass DM, Pletnikova O et al (2004) Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia. Neurology 63:538–542 source
- cites [40] Miki Y, Mori F, Hori E et al (2009) Hippocampal sclerosis with four-repeat tau-positive round inclusions in the dentate gyrus: a new type of four-repeat tauopathy. Acta Neuropathol 117:713–718 source
- cites [64] Zarow C, Sitzer TE, Chui HC (2008) Understanding hippocampal sclerosis in the elderly: epidemiology, characterization, and diagnostic issues. Curr Neurol Neurosci Rep 8:363–370 source
- Premisecitation
TDP-43 immunoreactive inclusions are commonly observed in cases with AD neuropathologic change.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [8] Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445 source
- cites [9] Arai T, Mackenzie IR, Hasegawa M et al (2009) Phosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies. Acta Neuropathol 117:125–136 source
- Premisecitation
TDP-43 immunoreactive inclusions are observed in the majority of cases of HS.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [8] Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445 source
- cites [28] Hatanpaa KJ, Blass DM, Pletnikova O et al (2004) Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia. Neurology 63:538–542 source
- cites [40] Miki Y, Mori F, Hori E et al (2009) Hippocampal sclerosis with four-repeat tau-positive round inclusions in the dentate gyrus: a new type of four-repeat tauopathy. Acta Neuropathol 117:713–718 source
- cites [64] Zarow C, Sitzer TE, Chui HC (2008) Understanding hippocampal sclerosis in the elderly: epidemiology, characterization, and diagnostic issues. Curr Neurol Neurosci Rep 8:363–370 source
- Premisecitation
TDP-43 immunoreactive inclusions are observed in most sporadic cases of amyotrophic lateral sclerosis.
“TDP-43 immunoreactive inclusions are observed in the majority of cases of HS (Figure 6) [8,28,40,64], about one-half of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8,9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [8] Amador-Ortiz C, Lin WL, Ahmed Z et al (2007) TDP-43 immunoreactivity in hippocampal sclerosis and Alzheimer’s disease. Ann Neurol 61:435–445 source
- cites [28] Hatanpaa KJ, Blass DM, Pletnikova O et al (2004) Most cases of dementia with hippocampal sclerosis may represent frontotemporal dementia. Neurology 63:538–542 source
- cites [40] Miki Y, Mori F, Hori E et al (2009) Hippocampal sclerosis with four-repeat tau-positive round inclusions in the dentate gyrus: a new type of four-repeat tauopathy. Acta Neuropathol 117:713–718 source
- cites [64] Zarow C, Sitzer TE, Chui HC (2008) Understanding hippocampal sclerosis in the elderly: epidemiology, characterization, and diagnostic issues. Curr Neurol Neurosci Rep 8:363–370 source
- May combine two claims. 2
- Classified as probably not a substantial claim. 1
May combine two claims.
PremisecitationRelatively isolated HS in very old individuals is associated with TDP-43-immunoreactive inclusions and with cognitive impairment.
“Relatively isolated HS may occur in very old individuals, and in this context it is associated with TDP-43-immunoreactive inclusions and with cognitive impairment [45,47].”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [45] Nelson PT, Abner EL, Schmitt FA et al (2010) Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons. Brain Pathol 20:66–79 source
The Discussion reports that hippocampal sclerosis (HS) was associated with lower MMSE scores and states that HS is associated with TDP-43 proteinopathy. The Results describe TDP-43-positive inclusions. Neither passage establishes these associations specifically for relatively isolated HS in very old individuals. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [47] Nelson PT, Schmitt FA, Lin Y et al (2011) Hippocampal sclerosis in advanced age: clinical and pathological features. Brain 134:1506–1518 source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationLBD occurs frequently in the olfactory bulb in older adults.
“Although not part of this classification scheme, it is important to realize that LBD also occurs frequently in the olfactory bulb in older adults and should be sampled when possible [20].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [20] Del Tredici K, Rub U, De Vos RA et al (2002) Where does Parkinson disease pathology begin in the brain? J Neuropathol Exp Neurol 61:413–426 source
May combine two claims.
PremisecitationNeuritic plaques appear closely associated with neuronal injury and are characterized by dystrophic neurites that frequently have phospho-tau immunoreactivity.
“A subset of senile plaques called neuritic plaques appear closely associated with neuronal injury and are characterized by the occurrence of dystrophic neurites that frequently have phospho-tau immunoreactivity [19,36,37,55].”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [19] DeKosky ST, Scheff SW (1990) Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol 27:457–464 source
- cites [36] Masliah E, Mallory M, Deerinck T et al (1993) Re-evaluation of the structural organization of neuritic plaques in Alzheimer’s disease. J Neuropathol Exp Neurol 52:619–632 source
- cites [37] Masliah E, Terry RD, Mallory M et al (1990) Diffuse plaques do not accentuate synapse loss in Alzheimer’s disease. Am J Pathol 137:1293–1297
- cites [55] Terry RD, Masliah E, Salmon DP et al (1991) Physical basis of cognitive alterations in Alzheimer’s disease: synapse loss is the major correlate of cognitive impairment. Ann Neurol 30:572–580 source
The paper relies on this without support.
Many other neurodegenerative disorders can cause dementia and may be co-morbid with AD neuropathologic change, especially in the elderly.
“There are many other neurodegenerative disorders that can cause dementia in addition to those discussed here, and any may be co-morbid with AD neuropathologic change, especially in the elderly.”
The paper relies on this without support.
Multiple diseases in the cerebrum can conspire to worsen cognitive symptoms.
“Multiple diseases in cerebrum can conspire to worsen cognitive symptoms; however, it often is difficult to judge the extent to which each disease observed at autopsy may have contributed to a given patient’s cognitive state.”
The paper relies on this without support.
Abnormal neuropil and neuronal cytoplasmic α-synuclein immunoreactivity are usually present with Lewy bodies but will not be apparent by H&E; in some instances, these changes occur in the absence of Lewy bodies.
“Abnormal neuropil and neuronal cytoplasmic α-synuclein immunoreactivity are usually present with LBs but will not be apparent by H&E; in some instances, these changes occur in the absence of LBs.”
The paper relies on this without support.
Diffuse white matter injury is a form of VBI but it is more difficult to judge objectively and is not specific to VBI.
“Diffuse white matter injury is a form of VBI but it is more difficult to judge objectively and is not specific to VBI.”
The paper relies on this without support.
Hippocampal sclerosis can be observed in the context of AD neuropathologic change, FTLD, and VBI, likely reflecting a heterogeneous etiology.
“HS can be observed in the context of AD neuropathologic change, frontotemporal lobar degeneration (FTLD), and VBI, likely reflecting a heterogeneous etiology.”
The paper relies on this without support.
Hippocampal sclerosis can be focal, so its absence in the recommended screening section does not rule out the possibility of HS elsewhere in the hippocampal formation.
“HS can be focal, thus its absence in the recommended screening section does not rule out the possibility of HS elsewhere in the hippocampal formation.”
The paper relies on this without support.
Hippocampal sclerosis can occur in several different diseases and has varying clinical implications in different settings.
“Clinico-pathological correlations need to recognize that HS can occur in several different diseases and has varying clinical implications in different settings.”
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 new NIA criteria use the same combination of moderate or frequent neuritic plaques and Braak stage III-VI as the minimum lesion density necessary for attributing the cause of dementia to AD.
“The new NIA criteria use the same combination of NPs and Braak stage as the minimum lesion density necessary for attributing the cause of dementia to AD (39, 40).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [40]
The Classification section says the new criteria use Braak stage and neuritic-plaque score, but also require an Aβ-plaque score as part of the ABC score. The Reporting section says intermediate or high AD neuropathologic change can adequately explain dementia; the passages do not establish moderate or frequent neuritic plaques plus Braak stage III–VI as the minimum sufficient combination. (LLM, conf=0.86)
Experimental — accuracy not yet measuredThe definitive diagnosis of Alzheimer's disease requires microscopic examination of multiple brain regions employing staining methods that can detect Alzheimer type neuropathologic change, with diagnosis based upon the morphology and density of lesions and their topographic distribution.
“The definitive diagnosis of AD requires microscopic examination of multiple brain regions employing staining methods that can detect Alzheimer type neuropathologic change [24], with diagnosis based upon the morphology and density of lesions and their topographic distribution.”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [24]
Nearly one third of patients with pathological findings of high likelihood Alzheimer's disease were thought to have other disorders, and 3% were considered clinically normal at the time of their last clinical exam.
“This finding is highlighted by the fact that nearly one third of patients with pathological findings of high likelihood Alzheimer’s disease [24] were thought to other disorders, and 3% were considered clinically normal at the time of their last clinical exam (Table 2).”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [24]
Both Aβ and paired helical filament (PHF) tau deposits are required to fulfill neuropathologic criteria for AD.
“However, both Aβ and paired helical filament (PHF) tau deposits are required to fulfill neuropathologic criteria for AD [105,106]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [105]
Autopsy analyses classified the level of ADNC from "none" to "high" using an established scoring system when available.
“Autopsy analyses classified the level of ADNC from “none” to “high” using an established scoring system when available.”
From Automatic classification of AD pathology in FTD phenotypes using natural speech (2024) · cites this paper as [30]
The Confirmed-AD group comprised 1854 participants who had a clinical Alzheimer dementia diagnosis and met criteria for ADNC at autopsy.
“Participants in the Confirmed-AD group (n ¼ 1854) were diagnosed with primary or contributing ADdementia at their last UDS visit before death and met our criteria for ADNC: moderate to frequent neuritic plaques and Braak stages III through VI, which loosely aligns with NIA-AA criteria for intermediate or high ADNC (13).”
From Concordance of Clinical Alzheimer Diagnosis and Neuropathological Features at Autopsy (2020) · cites this paper as [13]
The shortcomings of the NIA-Reagan criteria have been recognized and a revised set of criteria are currently in press.
“The shortcomings of the NIA-Reagan criteria have been recognized and a revised set of criteria are currently in press (39, 40).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [40]
In the revision of the 1997 criteria, combinations of plaque and tangle pathologies considered sufficient to cause dementia and qualify for the neuropathological diagnosis of AD are explicitly stated.
“In the revision of the 1997 criteria, combinations of plaque and tangle pathologies considered sufficient to cause dementia and qualify for the neuropathological diagnosis of AD are explicitly stated (40, 41).”
From Accuracy of the Clinical Diagnosis of Alzheimer Disease at National Institute on Aging Alzheimer Disease Centers, 2005–2010 (2012) · cites this paper as [40]
Neuropathological assessment used National Institute on Aging-Alzheimer Association diagnostic scoring guidelines.
“Neuropathological assessment was performed by 2 authors (T.G.B. and T.J.M.) blinded to clinical and imaging results and using NIA–AA diagnostic scoring guidelines.5,40”
From Positron Emission Tomography Imaging With [ <sup>18</sup> F]flortaucipir and Postmortem Assessment of Alzheimer Disease Neuropathologic Changes (2020) · cites this paper as [40]
Additional changes that may occur in AD brains, such as amyloid angiopathy, age-related brain atrophy, synaptic pathology, white matter rarefaction, granulovacuolar degeneration, neuron loss, TDP-43 proteinopathy, and neuroinflammation, may contribute to cognitive impairment but are not considered pathognomonic features of AD.
“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).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [3]
Dense and extensive neocortical NFTs are very consistently associated with dementia and are required to constitute high burden of AD neuropathologic change.
“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).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [3]
The current revision of the NIA-AA guidelines stipulates 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.
“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).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [3]
There is no universally applied rubric for CVD pathologic diagnosis.
“There is no universally applied rubric for CVD pathologic diagnosis, although the recent National Institute on Aging–Alzheimer’s Association criteria attempted to systematize neuropathologic assessment of this complex form of brain injury (3).”
From Correlation of Alzheimer Disease Neuropathologic Changes With Cognitive Status: A Review of the Literature (2012) · cites this paper as [3]
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Self-citationPhases of Aβ-deposition in the human brain and its relevance for the development of AD
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Self-citationSynapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
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“We recommend reporting all macroscopic VBI and enumerating microvascular lesions or MVLs (microscopic infarcts/hemorrhages) in standard screening sections [26, 51, 53, 60].”
Self-citationHYMAN, B. T., & TROJANOWSKI, J. Q. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199710000-00002 · Cited by 1,542 · see citing works
Self-citationCairns, N. J., Bigio, E. H., Mackenzie, I. R. A., Neumann, M., Lee, V. M.-Y., Hatanpaa, K. J., White, C. L., Schneider, J. A., Grinberg, L. T., Halliday, G., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0237-2 · Cited by 1,110 · cited 1× · see citing works
“We refer the reader to recent consensus guidelines for the neuropathologic evaluation of FTLD and its subtypes [17, 34, 35], and issues important in the distinction of AD neuropathologic change from those of some forms of FTLD [58].”
Self-citationMackenzie, I. R. A., Neumann, M., Bigio, E. H., Cairns, N. J., Alafuzoff, I., Kril, J., Kovacs, G. G., Ghetti, B., Halliday, G., Holm, I. E., et al. (2010) · Acta Neuropathologica · doi:10.1007/s00401-009-0612-2 · Cited by 1,012 · cited 1× · see citing works
“We refer the reader to recent consensus guidelines for the neuropathologic evaluation of FTLD and its subtypes [17, 34, 35], and issues important in the distinction of AD neuropathologic change from those of some forms of FTLD [58].”
Self-citationTDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador‐Ortiz, C., Lin, W., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff‐Radford, N. R., Hutton, M. L., & Dickson, D. W. (2007) · Annals of Neurology · doi:10.1002/ana.21154 · Cited by 916 · cited 1× · see citing works
“6) [8, 28, 40, 64], about onehalf of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8, 9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Self-citationWhere Does Parkinson Disease Pathology Begin in the Brain?
Del Tredici, K., Rüb, U., de Vos, R. A. I., Bohl, J. R. E., & Braak, H. (2002) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/61.5.413 · Cited by 773 · cited 1× · see citing works
“Although not part of this classification scheme, it is important to realize that LBD also occurs frequently in the olfactory bulb in older adults and should be sampled when possible [20].”
Hamilton, R. L. (2000) · Brain Pathology · doi:10.1111/j.1750-3639.2000.tb00269.x · Cited by 754 · cited 1× · see citing works
“LBs are frequent in the setting of moderate-to-severe levels of AD neuropathologic change [27, 59], including some early-onset familial AD cases [32, 33].”
The Pathogenesis of Senile Plaques
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“amyloid precursor protein, ubiquitin, neurofilament or phospho-tau, will identify specific, and partially overlapping, subtypes of dystrophic neurites that may differ in disease relevance [21].”
Self-citationthe Arizona Parkinson’s Disease Consortium, Beach, T. G., Adler, C. H., Lue, L., Sue, L. I., Bachalakuri, J., Henry-Watson, J., Sasse, J., Boyer, S., Shirohi, S., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0538-8 · Cited by 698 · cited 1× · see citing works
“For cases with incomplete clinical history, we note that ‘‘Neocortical LBD’’ is correlated with greater likelihood of cognitive impairment [1, 11–13, 22, 31–33, 38, 46, 49, 52].”
Self-citationCerebral amyloid angiopathy without and with cerebral hemorrhages: A comparative histological study
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“Although cerebral amyloid angiopathy (CAA) is not considered in the ‘‘ABC’’ score, it is very commonly observed in cases with parenchymal Ab plaques and should be evaluated and reported systematically as well as appreciated for its potential pathophysiological significance [56, 61].”
DLB and PDD boundary issues: Diagnosis, treatment, molecular pathology, and biomarkers
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Self-citationCo-morbidity of TDP-43 proteinopathy in Lewy body related diseases
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“6) [8, 28, 40, 64], about onehalf of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8, 9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Self-citationAlafuzoff, I., Arzberger, T., Al‐Sarraj, S., Bodi, I., Bogdanovic, N., Braak, H., Bugiani, O., Del‐Tredici, K., Ferrer, I., Gelpi, E., et al. (2008) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00147.x · Cited by 467 · cited 1× · see citing works
“While we do not propose specific protocols, our recommendations are compatible with conclusions by others who have optimized reproducibility of some neuropathologic assessments across multiple sites [2–5, 41].”
Self-citationPathological correlates of dementia in a longitudinal, population‐based sample of aging
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“Although there are some differences in approach, guidelines have emerged for clinico-pathologic correlation of MVLs: one MVL identified in standard sections of brain (Table 1 italicized regions) is of unclear relationship to cognitive function, while multiple MVLs in these regions are associated with increased likelih…”
Self-citationMackenzie, I. R., Neumann, M., Bigio, E. H., Cairns, N. J., Alafuzoff, I. I., Kril, J. J., Kovács, G. G., Ghetti, B. F., Halliday, G. M., Holm, I. E., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0460-5 · Cited by 418 · cited 1× · see citing works
“We refer the reader to recent consensus guidelines for the neuropathologic evaluation of FTLD and its subtypes [17, 34, 35], and issues important in the distinction of AD neuropathologic change from those of some forms of FTLD [58].”
Self-citationCerebral amyloid angiopathy and its relationship to Alzheimer’s disease
Thal, D. R., Griffin, W. S. T., de Vos, R. A. I., & Ghebremedhin, E. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0366-2 · Cited by 372 · cited 1× · see citing works
“Although cerebral amyloid angiopathy (CAA) is not considered in the ‘‘ABC’’ score, it is very commonly observed in cases with parenchymal Ab plaques and should be evaluated and reported systematically as well as appreciated for its potential pathophysiological significance [56, 61].”
Self-citationEvidence that incidental Lewy body disease is pre-symptomatic Parkinson’s disease
Dickson, D. W., Fujishiro, H., DelleDonne, A., Menke, J., Ahmed, Z., Klos, K. J., Josephs, K. A., Frigerio, R., Burnett, M., Parisi, J. E., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0345-7 · Cited by 364 · cited 1× · see citing works
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1, 49]; this may represent pre-clinical LBD [12, 22, 31].”
Self-citationAlzheimer Disease With Amygdala Lewy Bodies: A Distinct Form of α-Synucleinopathy
Uchikado, H., Lin, W.-L., DeLucia, M. W., & Dickson, D. W. (2006) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/01.jnen.0000225908.90052.07 · Cited by 359 · cited 2× · see citing works
“LBs are frequent in the setting of moderate-to-severe levels of AD neuropathologic change [27, 59], including some early-onset familial AD cases [32, 33].”
Self-citationVascular pathology in the aged human brain
Grinberg, L. T., & Thal, D. R. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0652-7 · Cited by 345 · cited 1× · see citing works
“CVD and vascular brain injury (VBI) [50] commonly are encountered in the brains with AD neuropathologic change [25].”
Self-citationPhosphorylated TDP-43 in Alzheimer’s disease and dementia with Lewy bodies
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“6) [8, 28, 40, 64], about onehalf of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8, 9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Neuropathologic Substrates of Ischemic Vascular Dementia
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“We recommend reporting all macroscopic VBI and enumerating microvascular lesions or MVLs (microscopic infarcts/hemorrhages) in standard screening sections [26, 51, 53, 60].”
Self-citationHippocampal sclerosis in advanced age: clinical and pathological features
Nelson, P. T., Schmitt, F. A., Lin, Y., Abner, E. L., Jicha, G. A., Patel, E., Thomason, P. C., Neltner, J. H., Smith, C. D., Santacruz, K. S., et al. (2011) · Brain · doi:10.1093/brain/awr053 · Cited by 279 · cited 1× · see citing works
“Relatively isolated HS may occur in very old individuals, and in this context it is associated with TDP-43–immunoreactive inclusions and with cognitive impairment [45, 47].”
Self-citationNelson, P. T., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Smith, C. D., Davis, D. G., Poduska, J. W., Patel, E., Mendiondo, M. S., et al. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00244.x · Cited by 239 · cited 1× · see citing works
“Relatively isolated HS may occur in very old individuals, and in this context it is associated with TDP-43–immunoreactive inclusions and with cognitive impairment [45, 47].”
Self-citationDifferent Patterns of Cerebral Injury in Dementia With or Without Diabetes
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“We recommend reporting all macroscopic VBI and enumerating microvascular lesions or MVLs (microscopic infarcts/hemorrhages) in standard screening sections [26, 51, 53, 60].”
Diffuse plaques do not accentuate synapse loss in Alzheimer's disease.
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Self-citationLinkage of the Indiana kindred of Gerstmann-Sträussler-Scheinker disease to the prion protein gene
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“Finally, not only can the neuropathologic changes of prion disease be co-morbid with AD, but some forms of prion disease can overlap with AD and need to be distinguished with special stains [23].”
Lewy Body-Related α-Synucleinopathy in Aging
Saito, Y., Ruberu, N. N., Sawabe, M., Arai, T., Kazama, H., Hosoi, T., Yamanouchi, H., & Murayama, S. (2004) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/63.7.742 · Cited by 200 · see citing works
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Assessment of β-amyloid deposits in human brain: a study of the BrainNet Europe Consortium
Alafuzoff, I., Thal, D. R., Arzberger, T., Bogdanovic, N., Al-Sarraj, S., Bodi, I., Boluda, S., Bugiani, O., Duyckaerts, C., Gelpi, E., et al. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0485-4 · Cited by 193 · cited 1× · see citing works
“While we do not propose specific protocols, our recommendations are compatible with conclusions by others who have optimized reproducibility of some neuropathologic assessments across multiple sites [2–5, 41].”
Self-citationEvaluation of α-synuclein immunohistochemical methods used by invited experts
Beach, T. G., White, C. L., Hamilton, R. L., Duda, J. E., Iwatsubo, T., Dickson, D. W., Leverenz, J. B., Roncaroli, F., Buttini, M., Hladik, C. L., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0409-8 · Cited by 182 · cited 2× · see citing works
“For cases with incomplete clinical history, we note that ‘‘Neocortical LBD’’ is correlated with greater likelihood of cognitive impairment [1, 11–13, 22, 31–33, 38, 46, 49, 52].”
Self-citationTDP-43 in aging and Alzheimer's disease - a review.
Wilson, A. C., Dugger, B. N., Dickson, D. W., & Wang, D.-S. (2011) · PubMed Central · Cited by 165 · see citing works
Self-citationCerebral Microinfarcts Associated with Severe Cerebral β‐Amyloid Angiopathy
Soontornniyomkij, V., Lynch, M. D., Mermash, S., Pomakian, J., Badkoobehi, H., Clare, R., & Vinters, H. V. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2009.00322.x · Cited by 153 · cited 1× · see citing works
“We recommend reporting all macroscopic VBI and enumerating microvascular lesions or MVLs (microscopic infarcts/hemorrhages) in standard screening sections [26, 51, 53, 60].”
Self-citationSelnes, O. A., & Vinters, H. V. (2006) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0294 · Cited by 146 · see citing works
Self-citationIncidental Lewy body disease: Clinical comparison to a control cohort
Adler, C. H., Connor, D. J., Hentz, J. G., Sabbagh, M. N., Caviness, J. N., Shill, H. A., Noble, B., & Beach, T. G. (2010) · Movement Disorders · doi:10.1002/mds.22971 · Cited by 143 · cited 1× · see citing works
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1, 49]; this may represent pre-clinical LBD [12, 22, 31].”
Self-citationLeverenz, J. B., Fishel, M. A., Peskind, E. R., Montine, T. J., Nochlin, D., Steinbart, E., Raskind, M. A., Schellenberg, G. D., Bird, T. D., & Tsuang, D. (2006) · Archives of Neurology · doi:10.1001/archneur.63.3.370 · Cited by 139 · see citing works
Self-citationReduced striatal tyrosine hydroxylase in incidental Lewy body disease
Beach, T. G., Adler, C. H., Sue, L. I., Peirce, J. B., Bachalakuri, J., Dalsing-Hernandez, J. E., Lue, L. F., Caviness, J. N., Connor, D. J., Sabbagh, M. N., et al. (2008) · Acta Neuropathologica · doi:10.1007/s00401-007-0313-7 · Cited by 128 · cited 1× · see citing works
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1, 49]; this may represent pre-clinical LBD [12, 22, 31].”
Self-citationAlafuzoff, I., Pikkarainen, M., Al-Sarraj, S., Arzberger, T., Bell, J., Bodi, I., Bogdanovic, N., Budka, H., Bugiani, O., Ferrer, I., et al. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000229986.17548.27 · Cited by 117 · cited 1× · see citing works
“LBs may be detected in neurons of medulla, pons and midbrain with hematoxylin and eosin (H&E)-stained sections; however, greater sensitivity can be achieved with immunohistochemistry for a-synuclein and this approach is strongly preferred [3, 4, 13].”
Self-citationNelson, P. T., Abner, E. L., Schmitt, F. A., Kryscio, R. J., Jicha, G. A., Santacruz, K., Smith, C. D., Patel, E., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181aacbe9 · Cited by 115 · cited 1× · see citing works
“[57] c Neuritic plaque score should be determined by the method of CERAD [41] d Medial temporal lobe NFTs in the absence of significant Ab or neuritic plaques occurs in older people and may be seen in individuals without cognitive impairment, with mild impairment, or with cognitive impairment from causes other than AD…”
Self-citationProdromal clinical manifestations of neuropathologically confirmed Lewy body disease
Jicha, G. A., Schmitt, F. A., Abner, E., Nelson, P. T., Cooper, G. E., Smith, C. D., & Markesbery, W. R. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.09.017 · Cited by 111 · cited 1× · see citing works
“Clinico-pathologic correlation for individuals without cognitive impairment should indicate that, although much less common than AD neuropathologic change, LBD has been observed in individuals without apparent cognitive or motor deficit [1, 49]; this may represent pre-clinical LBD [12, 22, 31].”
Self-citationRe-Evaluation of the Structural Organization of Neuritic Plaques in Alzheimerʼs Disease
MASLIAH, E., MALLORY, M., DEERINCK, T., DETERESA, R., LAMONT, S., MILLER, A., TERRY, R. D., CARRAGHER, B., & ELLISMAN, M. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00009 · Cited by 105 · see citing works
Self-citationZarow, C., Sitzer, T. E., & Chui, H. C. (2008) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-008-0057-3 · Cited by 104 · see citing works
Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies
Nelson, P. T., Kryscio, R. J., Jicha, G. A., Abner, E. L., Schmitt, F. A., Xu, L. O., Cooper, G., Smith, C. D., & Markesbery, W. R. (2009) · Neurology · doi:10.1212/wnl.0b013e3181bacf9e · Cited by 99 · cited 1× · see citing works
“For cases with incomplete clinical history, we note that ‘‘Neocortical LBD’’ is correlated with greater likelihood of cognitive impairment [1, 11–13, 22, 31–33, 38, 46, 49, 52].”
Self-citationAssessment of α-Synuclein Pathology: A Study of the BrainNet Europe Consortium
Alafuzoff, I., Parkkinen, L., Al-Sarraj, S., Arzberger, T., Bell, J., Bodi, I., Bogdanovic, N., Budka, H., Ferrer, I., Gelpi, E., et al. (2008) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181633526 · Cited by 90 · cited 1× · see citing works
“LBs may be detected in neurons of medulla, pons and midbrain with hematoxylin and eosin (H&E)-stained sections; however, greater sensitivity can be achieved with immunohistochemistry for a-synuclein and this approach is strongly preferred [3, 4, 13].”
Self-citationMost cases of dementia with hippocampal sclerosis may represent frontotemporal dementia
Hatanpaa, K. J., Blass, D. M., Pletnikova, O., Crain, B. J., Bigio, E. H., Hedreen, J. C., White, C. L., & Troncoso, J. C. (2004) · Neurology · doi:10.1212/01.wnl.0000129543.46734.c0 · Cited by 86 · see citing works
Self-citationNagy, Z., Yilmazer-Hanke, D. M., Braak, H., Braak, E., Schultz, C., & Hanke, J. (1998) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017038 · Cited by 51 · cited 1× · see citing works
“We recommend continued use of the staging scheme for neurofibrillary degeneration as described originally by Braak and Braak [14, 15], reduced to four stages (Table 2) that improves inter-rater reliability [42].”
Neuropathology of Hippocampal Sclerosis
Amador, C., & Dickson, D. W. (2008) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)01253-5 · Cited by 37 · cited 1× · see citing works
“Hippocampal sclerosis (HS) is defined by pyramidal cell loss and gliosis in CA1 and subiculum of the hippocampal formation that is out of proportion to AD neuropathologic change in the same structures [7].”
Self-citationUchihara, T., Nakamura, A., Yamazaki, M., Mori, O., Ikeda, K., & Tsuchiya, K. (2001) · Acta Neuropathologica · doi:10.1007/s004010100401 · Cited by 36 · cited 4× · see citing works
“HS can be observed in the context of AD neuropathologic change, frontotemporal lobar degeneration (FTLD), and VBI, likely reflecting a heterogeneous etiology.”
InfluentialMiki, Y., Mori, F., Hori, E., Kaimori, M., & Wakabayashi, K. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0531-2 · Cited by 29 · cited 1× · see citing works
“6) [8, 28, 40, 64], about onehalf of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8, 9] or with LBD [43], as well as other neurodegenerative diseases [48].”
TAR-DNA binding protein-43 and alterations in the hippocampus
Rauramaa, T. H., Pikkarainen, M., Englund, E. M., Ince, P. G., Jellinger, K. A., Paetau, A. E., & Alafuzoff, I. I. (2011) · Journal of Neural Transmission · doi:10.1007/s00702-010-0574-5 · Cited by 27 · cited 1× · see citing works
“6) [8, 28, 40, 64], about onehalf of cases with FTLD and ubiquitin inclusions with or without motor neuron disease, most sporadic cases of amyotrophic lateral sclerosis, and commonly in cases with AD neuropathologic change [8, 9] or with LBD [43], as well as other neurodegenerative diseases [48].”
Genetics of frontotemporal lobar degeneration
Mathuranath, P. S., Aswathy, P., & Jairani, P. (2010) · Annals of Indian Academy of Neurology · doi:10.4103/0972-2327.74246 · Cited by 5 · cited 1× · see citing works
“With the exception of individuals with mutations in TARDBP, GRN, VCP or c9ORF72 [10, 18], it is not clear whether TDP-43 proteinopathy in these other neurodegenerative diseases is”
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NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish, J., et al. (2018) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2018.02.018 · Cited by 10,537 · see citing works
“It is worthwhile emphasizing that, like the 2012 NIA-AA classification system for AD neuropathic change [105,106], AT(N) scoring of biomarkers is independent from clinical symptoms.”
Self-citationDiagnosis and management of dementia with Lewy bodies: Fourth consensus report of the DLB Consortium
McKeith, I. G., Boeve, B. F., Dickson, D. W., Halliday, G., Taylor, J.-P., Weintraub, D., Aarsland, D., Galvin, J., Attems, J., Ballard, C. G., et al. (2017) · Neurology · doi:10.1212/wnl.0000000000004058 · Cited by 4,476 · see citing works
Self-citationThe neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329 · see citing works
“methods that can detect Alzheimer type neuropathologic change [24], with diagnosis based upon the morphology and density of lesions and their topographic distribution.”
BackgroundMethodInfluentialSelf-citationRevised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup
Jack, C. R., Andrews, J. S., Beach, T. G., Buracchio, T., Dunn, B., Graf, A., Hansson, O., Ho, C., Jagust, W., McDade, E., et al. (2024) · Alzheimer's & Dementia · doi:10.1002/alz.13859 · Cited by 2,803 · see citing works
Self-citationKnopman, D. S., Amieva, H., Petersen, R. C., Chételat, G., Holtzman, D. M., Hyman, B. T., Nixon, R. A., & Jones, D. T. (2021) · Nature Reviews Disease Primers · doi:10.1038/s41572-021-00269-y · Cited by 2,606 · see citing works
Self-citationThe spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
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Self-citationDefeating Alzheimer's disease and other dementias: a priority for European science and society
Winblad, B., Amouyel, P., Andrieu, S., Ballard, C., Brayne, C., Brodaty, H., Cedazo-Minguez, A., Dubois, B., Edvardsson, D., Feldman, H., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)00062-4 · Cited by 1,676 · see citing works
Pathology of Neurodegenerative Diseases
Dugger, B. N., & Dickson, D. W. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028035 · Cited by 1,665 · see citing works
“The most recent revision of neuropathological criteria (Montine et al. 2012) includes an assessment of topographic distribution rather than density of amyloid deposits using a staging scheme proposed by Thalet al. (2002).”
BackgroundMethodInfluentialSelf-citationLimbic-predominant age-related TDP-43 encephalopathy (LATE): consensus working group report
Nelson, P. T., Dickson, D. W., Trojanowski, J. Q., Jack, C. R., Boyle, P. A., Arfanakis, K., Rademakers, R., Alafuzoff, I., Attems, J., Brayne, C., et al. (2019) · Brain · doi:10.1093/brain/awz099 · Cited by 1,547 · see citing works
Self-citationPrimary age-related tauopathy (PART): a common pathology associated with human aging
Crary, J. F., Trojanowski, J. Q., Schneider, J. A., Abisambra, J. F., Abner, E. L., Alafuzoff, I., Arnold, S. E., Attems, J., Beach, T. G., Bigio, E. H., et al. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1349-0 · Cited by 1,467 · see citing works
“the current guidelines for AD [64, 102], mild Aβ plaques”
BackgroundInfluentialSelf-citationFunctional aspects of meningeal lymphatics in ageing and Alzheimer’s disease
Da Mesquita, S., Louveau, A., Vaccari, A., Smirnov, I., Cornelison, R. C., Kingsmore, K. M., Contarino, C., Onengut-Gumuscu, S., Farber, E., Raper, D., et al. (2018) · Nature · doi:10.1038/s41586-018-0368-8 · Cited by 1,445 · see citing works
Beach, T. G., Monsell, S. E., Phillips, L. E., & Kukull, W. (2012) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e31824b211b · Cited by 1,103 · see citing works
“The new NIA criteria use this same combination of NPs and Braak stage as the minimum lesion density necessary for attributing the cause of dementia to AD (39, 40).”
BackgroundMethodSelf-citationClinicopathological evaluation of chronic traumatic encephalopathy in players of American football
Mez, J., Daneshvar, D. H., Kiernan, P. T., Abdolmohammadi, B., Alvarez, V. E., Huber, B. R., Alosco, M. L., Solomon, T. M., Nowinski, C. J., McHale, L., et al. (2017) · JAMA · doi:10.1001/jama.2017.8334 · Cited by 1,098 · see citing works
Blümcke, I., Thom, M., Aronica, E., Armstrong, D. D., Bartoloméi, F., Bernasconi, A., Bernasconi, N., Bien, C. G., Cendes, F., Coras, R., et al. (2013) · Epilepsia · doi:10.1111/epi.12220 · Cited by 1,010 · see citing works
“Segmental hippocampal neuron loss can be also observed in other pathologic conditions, including dementia, aging, ischemia, and neurodegeneration, but the patterns of neuronal cell loss may differ and usually also involves the subiculum (Nelson et al., 2011; Montine et al., 2012).”
Backgroundthe TBI/CTE group, McKee, A. C., Cairns, N. J., Dickson, D. W., Folkerth, R. D., Dirk Keene, C., Litvan, I., Perl, D. P., Stein, T. D., Vonsattel, J.-P., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1515-z · Cited by 885 · see citing works
“Of the NIA-AA sampling guidelines, the following blocks are most valuable for detecting CTE: sulcal depths of the superior and middle frontal gyrus, superior and middle temporal gyrus and inferior parietal gyrus (Fig.”
BackgroundMethodInfluentialSelf-citationParkinson's disease dementia: convergence of α-synuclein, tau and amyloid-β pathologies
Irwin, D. J., Lee, V. M. ‐., & Trojanowski, J. Q. (2013) · Nature reviews. Neuroscience · doi:10.1038/nrn3549 · Cited by 875 · see citing works
Self-citationAlzheimer's disease: experimental models and reality
Drummond, E., & Wisniewski, T. (2017) · Acta Neuropathologica · doi:10.1007/s00401-016-1662-x · Cited by 810 · see citing works
“The current consensus guidelines for neuropathological evaluation of AD are ranked on three parameters (Amyloid, Braak and CERAD staging) to obtain an “ABC” score that quantifies both neuritic plaques and NFT pathology [65, 99].”
MethodLópez, J. A., González, H. M., & Léger, G. C. (2019) · Handbook of clinical neurology · doi:10.1016/b978-0-12-804766-8.00013-3 · Cited by 834 · see citing works
Proteopathic tau seeding predicts tauopathy in vivo
Holmes, B. B., Furman, J. L., Mahan, T. E., Yamasaki, T. R., Mirbaha, H., Eades, W. C., Belaygorod, L., Cairns, N. J., Holtzman, D. M., & Diamond, M. I. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411649111 · Cited by 696 · see citing works
Self-citationWebster, S. J., Bachstetter, A. D., Nelson, P. T., Schmitt, F. A., & Van Eldik, L. J. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00088 · Cited by 755 · see citing works
“In 2012, new consensus guidelines for neuropathologic evaluation of AD were adopted (Hyman et al., 2012; Montine et al., 2012).”
Self-citationRobinson, J. L., Lee, E. B., Xie, S. X., Rennert, L., Suh, E., Bredenberg, C., Caswell, C., Van Deerlin, V. M., Yan, N., Yousef, A., et al. (2018) · Brain · doi:10.1093/brain/awy146 · Cited by 729 · see citing works
Self-citationIranzo, Á., Tolosa, E. S., Gelpí, E., Molinuevo, J. L., Valldeoriola, F., Serradell, M., Sánchez‐Valle, R., Vilaseca, I., Lomeña, F., Vilas, D., et al. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70056-5 · Cited by 729 · see citing works
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New insights into atypical Alzheimer's disease in the era of biomarkers
Graff-Radford, J., Yong, K. X. X., Apostolova, L. G., Bouwman, F. H., Carrillo, M., Dickerson, B. C., Rabinovici, G. D., Schott, J. M., Jones, D. T., & Murray, M. E. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(20)30440-3 · Cited by 706 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
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Self-citationThijssen, E. H., La Joie, R., Strom, A., Fonseca, C., Iaccarino, L., Wolf, A., Spina, S., Allen, I. E., Cobigo, Y., Heuer, H., et al. (2021) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00214-3 · Cited by 607 · see citing works
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“All cases used had been examined histologically and the diagnosis reached using internationally accepted criteria.(18) Initial 10% w/v brain homogenates were prepared using phosphate-buffered saline (PBS) containing 1 mmol/L EDTA, 150 mmol/L NaCl, 0.”
MethodJohnson, K. A., Minoshima, S., Bohnen, N. I., Donohoe, K. J., Foster, N. L., Herscovitch, P., Karlawish, J. H., Rowe, C. C., Carrillo, M. C., Hartley, D. M., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.01.002 · Cited by 603 · see citing works
Irwin, D. J., Grossman, M., Weintraub, D. A., Hurtig, H. I., Duda, J. E., Xie, S. X., Lee, E. B., Deerlin, V. M. V., López, O. L., Kofler, J., et al. (2016) · The Lancet Neurology · doi:10.1016/s1474-4422(16)30291-5 · Cited by 588 · see citing works
Self-citationOssenkoppele, R., Pijnenburg, Y. A. L., Perry, D. C., Cohn-Sheehy, B. I., Scheltens, N. M. E., Vogel, J. W., Kramer, J. H., van der Vlies, A. E., Joie, R. L., Rosen, H. J., et al. (2015) · Brain · doi:10.1093/brain/awv191 · Cited by 548 · see citing works
“All had stage V and thus classified for ‘high’ Alzheimer’s disease neuropathological change according to recently proposed NIA-AA guidelines (Montine et al., 2012).”
BackgroundMethodPreclinical Alzheimer's disease and its outcome: a longitudinal cohort study
Vos, S. J., Xiong, C., Visser, P. J., Jasielec, M. S., Hassenstab, J., Grant, E. A., Cairns, N. J., Morris, J. C., Holtzman, D. M., & Fagan, A. M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70194-7 · Cited by 564 · see citing works
Self-citationJohnson, E. C. B., Carter, E. K., Dammer, E. B., Duong, D. M., Gerasimov, E. S., Liu, Y., Liu, J., Betarbet, R., Ping, L., Yin, L., et al. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-00999-y · Cited by 561 · see citing works
“Cases were defined based on a unified classification scheme using semi-quantitative histopathological measures of A β and tau neurofibrillary tangle deposition 12–15 as well as cognitive function near time of death, as previously described 7 .”
Self-citationThe preclinical phase of the pathological process underlying sporadic Alzheimer’s disease
Braak, H., & Del Tredici, K. (2015) · Brain · doi:10.1093/brain/awv236 · Cited by 540 · see citing works
“susceptible proteins Aggregates consisting of two different pathological proteins, abnormal tau and amyloid-b, are central to the process underlying Alzheimer’s disease (Duyckaerts et al., 2009; Montine et al., 2012; Nelson et al., 2012; Spillantini and Goedert, 2013).”
BackgroundInfluentialMolecular characterization of selectively vulnerable neurons in Alzheimer’s disease
Leng, K., Li, E., Eser, R., Piergies, A., Sit, R., Tan, M., Neff, N., Li, S. H., Rodriguez, R. D., Suemoto, C. K., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00764-7 · Cited by 485 · see citing works
Reduced glucocerebrosidase is associated with increased α-synuclein in sporadic Parkinson’s disease
Murphy, K. E., Gysbers, A. M., Abbott, S. K., Tayebi, N., Kim, W. S., Sidransky, E., Cooper, A., Garner, B., & Halliday, G. M. (2014) · Brain · doi:10.1093/brain/awt367 · Cited by 475 · see citing works
An autoradiographic evaluation of AV-1451 Tau PET in dementia
Lowe, V. J., Curran, G., Fang, P., Liesinger, A. M., Josephs, K. A., Parisi, J. E., Kantarci, K., Boeve, B. F., Pandey, M. K., Bruinsma, T., et al. (2016) · Acta Neuropathologica Communications · doi:10.1186/s40478-016-0315-6 · Cited by 474 · see citing works
“To examine binding specificity of AV-1451 to tau we included neuropathologically normal individuals with no NFT or Aβ deposits (n = 3), neuropathologically normal individuals with minimal NFT and substantial Aβ deposits ((“pathological aging” (PA), n = 2), neuropathologically normal individuals with NFT and no Aβ depo…”
BackgroundSelf-citationModeling Alzheimer’s disease with iPSC-derived brain cells
Penney, J., Ralvenius, W. T., & Tsai, L.-H. (2020) · Molecular Psychiatry · doi:10.1038/s41380-019-0468-3 · Cited by 471 · see citing works
Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Dujardin, S., Commins, C., Lathuiliere, A., Beerepoot, P., Fernandes, A. R., Kamath, T. V., De Los Santos, M. B., Klickstein, N., Corjuc, D. L., Corjuc, B. T., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0938-9 · Cited by 438 · see citing works
Self-citationBeach, T. G., Adler, C. H., Sue, L. I., Serrano, G., Shill, H. A., Walker, D. G., Lue, L., Roher, A. E., Dugger, B. N., Maarouf, C., et al. (2015) · Neuropathology · doi:10.1111/neup.12189 · Cited by 460 · see citing works
“We are currently engaged in retrospectively rating a subset of past cases for Thal amyloid phase,(86) and re-classifying the same subset according to NIA-AA (National Institute on Aging-Alzheimer’s Association) criteria for AD.(104,105) Paraffin sections stained with IHC for phosphorylated α-synuclein(70,82) are grade…”
MethodInfluentialSelf-citationRare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease
Cruchaga, C., Karch, C. M., Jin, S. C., Benitez, B. A., Cai, Y., Guerreiro, R., Harari, O., Norton, J., Budde, J., Bertelsen, S., et al. (2014) · Nature · doi:10.1038/nature12825 · Cited by 461 · see citing works
Self-citationNeuropathologic substrates of Parkinson disease dementia
Irwin, D. J., White, M. T., Toledo, J. B., Xie, S. X., Robinson, J. L., Van Deerlin, V., Lee, V. M. ‐., Leverenz, J. B., Montine, T. J., Duda, J. E., et al. (2012) · Annals of Neurology · doi:10.1002/ana.23659 · Cited by 518 · see citing works
“Cerebrovascular disease (CVD) was defined based on the presence of vascular brain injury (VBI) using modified criteria outlined in the latest National Institute on Aging (NIA)-Alzheimer’s Association (AA) guidelines.(38) Briefly, gross evidence of ischemic or hemorrhagic infarction or 2 or more microvascular lesions (…”
MethodSelf-citationKalaria, R. N. (2016) · Acta Neuropathologica · doi:10.1007/s00401-016-1571-z · Cited by 441 · see citing works
Rossi, M., Candelise, N., Baiardi, S., Capellari, S., Giannini, G., Orru, C. D., Antelmi, E., Mammana, A., Hughson, A. G., Buonaura, G. C., et al. (2020) · Acta Neuropathologica · doi:10.1007/s00401-020-02160-8 · Cited by 457 · see citing works
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Self-citationVilleneuve, S., Rabinovici, G. D., Cohn-Sheehy, B. I., Madison, C., Ayakta, N., Ghosh, P. M., La Joie, R., Arthur-Bentil, S. K., Vogel, J. W., Marks, S. M., et al. (2015) · Brain · doi:10.1093/brain/awv112 · Cited by 408 · see citing works
Distinct amyloid-β and tau-associated microglia profiles in Alzheimer’s disease
Gerrits, E., Brouwer, N., Kooistra, S. M., Woodbury, M. E., Vermeiren, Y., Lambourne, M., Mulder, J., Kummer, M., Möller, T., Biber, K., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-021-02263-w · Cited by 441 · see citing works
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“Those guidelines recommend that the 7-level staging scheme is reduced to a 4-level one, with stages I– II, III–IV and V–VI, respectively, combined for improved reliability (Montine et al., 2012).”
BackgroundMethodGroveman, B. R., Orru, C. D., Hughson, A. G., Raymond, L. D., Zanusso, G., Ghetti, B. F., Campbell, K. J., Safar, J., Galasko, D. R., & Caughey, B. W. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0508-2 · Cited by 414 · see citing works
“Pathological diagnoses of AD and DLB are made using National Institute on Aging-Alzheimer’s Association (NIA-AA) guidelines [22].”
Multimodal deep learning for Alzheimer's disease dementia assessment
Qiu, S., Miller, M. I., Joshi, P. S., Lee, J. C., Xue, C., Ni, Y., Wang, Y., De Anda-Duran, I., Hwang, P. H., Cramer, J. A., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-31037-5 · Cited by 420 · see citing works
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Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
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Integrated multimodal cell atlas of Alzheimer’s disease
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“Donors with any level of Lewy body dementia (LBD), vascular pathology or limbic-predominant age-related TDP-43 encephalopathy (LATE) were included because these conditions are common comorbidities in AD 39,40 .”
COVID-19 neuropathology at Columbia University Irving Medical Center/New York Presbyterian Hospital
Thakur, K. T., Miller, E. H., Glendinning, M. D., Al‐Dalahmah, O., Banu, M. A., Boehme, A. K., Boubour, A., Bruce, S. S., Chong, A. M., Claassen, J., et al. (2021) · Brain · doi:10.1093/brain/awab148 · Cited by 385 · see citing works
Melanopsin retinal ganglion cell loss in A lzheimer disease
Morgia, C. L., Ross‐Cisneros, F. N., Koronyo, Y., Hannibal, J., Gallassi, R., Cantalupo, G., Sambati, L., Pan, B. X., Tozer, K. R., Barboni, P., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24548 · Cited by 389 · see citing works
Dementia with Lewy bodies: an update and outlook
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“Unsurprisingly, such cases usually show additional high levels of AD neuropathological change [24, 25].”
BackgroundSystematic Review on Resting-State EEG for Alzheimer’s Disease Diagnosis and Progression Assessment
Cassani, R., Estarellas, M., San-Martin, R., Fraga, F. J., & Falk, T. H. (2018) · Disease Markers · doi:10.1155/2018/5174815 · Cited by 388 · see citing works
“Additionally, other disorders that also lead to dementia as vascular brain injury, Lewy body diseases, and Parkinson disease in some cases are also comorbid to AD [25].”
BackgroundNeuropathology of Alzheimer's Disease
Trejo‐Lopez, J. A., Yachnis, A. T., & Prokop, S. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01146-y · Cited by 398 · see citing works
“1 3 Braak stages were condensed into a 3-tier system with “B1” corresponding to Braak stages I and II, “B2” corresponding to Braak stages III and IV, and “B3” encompassing Braak stages V and VI [9, 10].”
BackgroundMethodInfluentialBrickman, A. M., Manly, J. J., Honig, L. S., Sanchez, D., Reyes‐Dumeyer, D., Lantigua, R. A., Lao, P. J., Stern, Y., Vonsattel, J. P., Teich, A. F., et al. (2021) · Alzheimer's & Dementia · doi:10.1002/alz.12301 · Cited by 387 · see citing works
Updated TDP-43 in Alzheimer’s disease staging scheme
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“The basal forebrain and insula cortex, for example, are well known to be affected by tau immunoreactive neurofibrillary tangle pathology in Alzheimer’s disease [9, 34].”
Self-citationAPOE4 homozygosity represents a distinct genetic form of Alzheimer’s disease
Fortea, J., Pegueroles, J., Alcolea, D., Belbin, O., Dols-Icardo, O., Vaqué-Alcázar, L., Videla, L., Gispert, J. D., Suárez-Calvet, M., Johnson, S. C., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02931-w · Cited by 369 · see citing works
Prevalence of mixed pathologies in the aging brain
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Structural imaging of hippocampal subfields in healthy aging and Alzheimer’s disease
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“28), the BB stages of neurofibrillary degeneration, CERAD score, and the level of AD-neuropathologic change [64] (for all Spearman correlation, p < 0.”
BackgroundMethodPathology and pathogenesis of vascular cognitive impairment—a critical update
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Corces, M. R., Shcherbina, A., Kundu, S., Gloudemans, M. J., Frésard, L., Granja, J. M., Louie, B. H., Eulalio, T., Shams, S., Bagdatli, S. T., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-00721-x · Cited by 358 · see citing works
Self-citationPhosphorylation of different tau sites during progression of Alzheimer’s disease
Neddens, J., Temmel, M., Flunkert, S., Kerschbaumer, B., Hoeller, C., Loeffler, T., Niederkofler, V., Daum, G., Attems, J., & Hutter-Paier, B. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0557-6 · Cited by 384 · see citing works
“internationally accepted criteria [31] (Table 1).”
Phosphorylated tau interactome in the human Alzheimer's disease brain
Drummond, E., Pires, G., MacMurray, C., Askenazi, M., Nayak, S., Bourdon, M., Safar, J., Ueberheide, B., & Wisniewski, T. (2020) · Brain · doi:10.1093/brain/awaa223 · Cited by 357 · see citing works
Immune Signaling in Neurodegeneration
Hammond, T. R., Marsh, S. E., & Stevens, B. (2019) · Immunity · doi:10.1016/j.immuni.2019.03.016 · Cited by 336 · see citing works
“tau, although both eventually heavily impact neocortical, entorhinal cortex, and hippocampal regions (for review and further description see (Braak and Braak, 1991; Montine et al., 2012)).”
BackgroundOlfactory bulb involvement in neurodegenerative diseases
Attems, J., Walker, L., & Jellinger, K. A. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1261-7 · Cited by 341 · see citing works
Murray, M. E., Lowe, V. J., Graff-Radford, N. R., Liesinger, A. M., Cannon, A., Przybelski, S. A., Rawal, B., Parisi, J. E., Petersen, R. C., Kantarci, K., et al. (2015) · Brain · doi:10.1093/brain/awv050 · Cited by 324 · see citing works
“…brains by retrospectively assessing senile plaque quantification of neocortex (i.e. midfrontal, inferior parietal or superior temporal cortex) and hippocampus using thioflavin-S staining results as supported in the latest NIA-AA recommendations (Hyman et al., 2012; Montine et al., 2012).”
BackgroundMethodInfluentialSelf-citationMesulam, M.-M., Weintraub, S., Rogalski, E. J., Wieneke, C., Geula, C., & Bigio, E. H. (2014) · Brain · doi:10.1093/brain/awu024 · Cited by 334 · see citing works
Self-citationPrognosis and neuropathologic correlation of clinical subtypes of Parkinson disease
De Pablo-Fernández, E., Lees, A. J., Holton, J. L., & Warner, T. T. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2018.4377 · Cited by 332 · see citing works
Moloney, C. M., Lowe, V. J., & Murray, M. E. (2021) · Alzheimer s & Dementia · doi:10.1002/alz.12321 · Cited by 337 · see citing works
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Bieniek, K. F., Cairns, N. J., Crary, J. F., Dickson, D. W., Folkerth, R. D., Keene, C. D., Litvan, I., Perl, D. P., Stein, T. D., Vonsattel, J., et al. (2021) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlab001 · Cited by 334 · see citing works
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“Together with the classical semiquantitative scoring of neuritic plaques [68], the Braak stages and Thal phases are included in the recent NIA-AA neuropathological criteria for AD [69].”
BackgroundSkrobot, O. A., Attems, J., Esiri, M. M., Hortobágyi, T., Ironside, J. W., Kalaria, R. N., King, A., Lammie, G. A., Mann, D. M. A., Neal, J., et al. (2016) · Brain · doi:10.1093/brain/aww214 · Cited by 323 · see citing works
“…to identify and categorize different types of cerebrovascular pathology in relation to dementia (Esiri et al., 1997; Chalmers et al., 2003; Kalaria et al., 2004; Love, 2005; Strozyk et al., 2010; Deramecourt et al., 2012; Montine et al., 2012; Richardson et al., 2012; Smallwood et al., 2012).”
BackgroundJack, C. R., Therneau, T. M., Weigand, S. D., Wiste, H. J., Knopman, D. S., Vemuri, P., Lowe, V. J., Mielke, M. M., Roberts, R. O., Machulda, M. M., et al. (2019) · JAMA Neurology · doi:10.1001/jamaneurol.2019.1971 · Cited by 300 · see citing works
PART is part of Alzheimer disease
Duyckaerts, C. J., Braak, H., Brion, J., Buée, L., Tredici, K. D., Goedert, M., Halliday, G. M., Neumann, M., Spillantini, M. G., Tolnay, M., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1390-7 · Cited by 316 · see citing works
“In conclusion, both Aβ and tau pathologies are necessary for the diagnosis of AD according to current criteria [17, 22].”
BackgroundMethodInfluentialSelf-citationLewczuk, P., Riederer, P. F., O’Bryant, S. E., Verbeek, M. M., Dubois, B., Visser, P. J., Jellinger, K. A., Engelborghs, S., Ramı́rez, A., Parnetti, L., et al. (2017) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1375556 · Cited by 308 · see citing works
“The recent NIA-AA guidelines consider levels of AD pathology regardless of the clinical history (Montine et al. 2012).”
BackgroundSelf-citationWu, Z., Guo, Z., Gearing, M., & Chen, G. (2014) · Nature Communications · doi:10.1038/ncomms5159 · Cited by 306 · see citing works
Suspected non-Alzheimer disease pathophysiology — concept and controversy
Jack, C. R., Knopman, D. S., Chételat, G., Dickson, D. W., Fagan, A. M., Frisoni, G. B., Jagust, W. J., Mormino, E. C., Petersen, R. C., Sperling, R. A., et al. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.251 · Cited by 299 · see citing works
“Third, the neuropathological definition of AD requires both Aβ and tau pathology 58,59 .”
Self-citationHall, H., Reyes, S., Landeck, N., Bye, C. R., Leanza, G., Double, K. L., Thompson, L. H., Halliday, G. M., & Kirik, D. (2014) · Brain · doi:10.1093/brain/awu193 · Cited by 306 · see citing works
“For this purpose, we selected cases not reaching current neuropathological criteria for any neurodegenerative condition other than Parkinson’s disease (Hyman et al., 2012; Montine et al., 2012) and analysed in detail selected brain regions in post-mortem material obtained from longitudinally followed demented and non-…”
BackgroundMethodBiomarker modeling of Alzheimer’s disease using PET-based Braak staging
Therriault, J., Pascoal, T. A., Lussier, F. Z., Tissot, C., Chamoun, M., Bezgin, G., Servaes, S., Benedet, A. L., Ashton, N. J., Karikari, T. K., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00204-0 · Cited by 308 · see citing works
“Unique (2) the correspondence with existing gold-standard histopathological frameworks for AD diagnosis 6,7 .”
InfluentialTesta, G., Staurenghi, E., Zerbinati, C., Gargiulo, S., Iuliano, L., Giaccone, G., Fantò, F., Poli, G., Leonarduzzi, G., & Gamba, P. (2016) · Redox Biology · doi:10.1016/j.redox.2016.09.001 · Cited by 293 · see citing works
“Definitive diagnosis requires post-mortem evaluation of NFT and senile plaques in the brain [9,10].”
De Schepper, S., Ge, J. Z., Sierksma, A., Crowley, G., Ferreira, L. S. S., Garceau, D., Toomey, C. E., Sokolova, D., Rueda-Carrasco, J., Shin, S.-H., et al. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01257-z · Cited by 295 · see citing works
“The level of AD pathology in all cases was assessed using current diagnostic consensus criteria 79,80 .”
Neuropathology and biochemistry of Aβ and its aggregates in Alzheimer’s disease
Thal, D. R., Walter, J., Saido, T. C., & Fändrich, M. (2015) · Acta Neuropathologica · doi:10.1007/s00401-014-1375-y · Cited by 319 · see citing works
Self-citationMonoaminergic neuropathology in Alzheimer’s disease
Šimić, G., Leko, M. B., Wray, S., Harrington, C. R., Delalle, I., Milošević, N. J., Bažadona, D., Buée, L., de Silva, R., Giovanni, G. D., et al. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.04.001 · Cited by 289 · see citing works
“The fourth part of the NIA/AA guidelines (Hyman et al., 2012; Montine et al., 2012) updated the 1997 NIA/Reagan Institute neuropathological criteria for AD (Hyman and Trojanowski, 1997).”
InfluentialBeta-amyloid deposition in chronic traumatic encephalopathy
Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1435-y · Cited by 291 · see citing works
“Subjects with AD changes had a low degree of neuropathological change as defined by the ABC score [15, 34].”
BackgroundComorbid neuropathological diagnoses in early versus late-onset Alzheimer's disease
Spina, S., La Joie, R., Petersen, C., Nolan, A. L., Cuevas, D., Cosme, C., Hepker, M., Hwang, J.-H., Miller, Z. A., Huang, E. J., et al. (2021) · Brain · doi:10.1093/brain/awab099 · Cited by 278 · see citing works
Xia, C., Makaretz, S. J., Caso, C., McGinnis, S. M., Gomperts, S. N., Sepulcre, J., Gómez‐Isla, T., Hyman, B. T., Schultz, A. P., Vasdev, N., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2016.5755 · Cited by 279 · see citing works
Self-citationAttems, J., Toledo, J. B., Walker, L., Gelpí, E., Gentleman, S., Halliday, G. M., Hortobágyi, T., Jellinger, K. A., Kovács, G. G., Lee, E. B., et al. (2021) · Acta Neuropathologica · doi:10.1007/s00401-020-02255-2 · Cited by 286 · see citing works
Self-citationMcAleese, K. E., Walker, L., Graham, S., Moya, E. L. J., Johnson, M. A., Erskine, D., Colloby, S. J., Dey, M., Martin-Ruiz, C. M., Taylor, J., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1738-2 · Cited by 271 · see citing works
“1 3 (NIA-AA) criteria [44] that included assessment of Thal phases of Aβ deposition [57], Braak staging of neurofibrillary pathology [10] and Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) scoring [43].”
MethodTherriault, J., Vermeiren, M. R., Servaes, S., Tissot, C., Ashton, N. J., Benedet, A. L., Karikari, T. K., Lantero‐Rodriguez, J., Brum, W. S., Lussier, F. Z., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.4485 · Cited by 268 · see citing works
Duration of American Football Play and Chronic Traumatic Encephalopathy
Mez, J., Daneshvar, D. H., Abdolmohammadi, B., Chua, A. S., Alosco, M. L., Kiernan, P. T., Evers, L., Marshall, L., Martin, B. M., Palmisano, J. N., et al. (2020) · Annals of Neurology · doi:10.1002/ana.25611 · Cited by 271 · see citing works
“Concussion definition provided 45 (12-150) 0 47.”
Novel advances in shotgun lipidomics for biology and medicine
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“AD is characterized clinically by progressive cognitive impairment [174] and neuropathologically by the appearance of diffusible amyloid-beta (Aβ), neuritic plaques, and intraneuronal neurofibrillary tangles [175].”
BackgroundUnger, M. S., Li, E., Scharnagl, L., Poupardin, R., Altendorfer, B., Mrowetz, H., Hutter-Paier, B., Weiger, T. M., Heneka, M. T., Attems, J., et al. (2020) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.05.070 · Cited by 248 · see citing works
Aging, Cellular Senescence, and Alzheimer’s Disease
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“Accumulation of β-amyloid (Aβ) peptides in the brain is a pathological feature of AD [44,45].”
BackgroundInfluential
- Authors
- Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., Nelson, P. T., Schneider, J. A., Thal, D. R., Trojanowski, J. Q., Vinters, H. V., & Hyman, B. T.
- Affiliations
- University of Washington (US)
- National Institutes of Health (US)
- Banner Sun Health Research Institute (US)
- Northwestern University (US)
- Washington University in St. Louis (US)
- Mayo Clinic (US)
- Pitié-Salpêtrière Hospital (FR)
- Harvard University (US)
- University of California San Diego (US)
- SUNY Downstate Health Sciences University (US)
- University of Kentucky (US)
- Rush University Medical Center (US)
- Universität Ulm (DE)
- University of Pennsylvania (US)
- University of California, Los Angeles (US)
- Corresponding author
- Montine, Thomas J.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2011-11-20
- Volume
- 123
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC3268003
- OpenAlex
- W2128228199
- Cited by
- 2,992
- References
- 66
- Citations by year
- 2026: 172 · 2025: 289 · 2024: 336 · 2023: 259 · 2022: 296 · 2021: 262 · 2020: 244 · 2019: 187 · 2018: 164 · 2017: 146 · 2016: 141 · 2015: 135 · 2014: 92 · 2013: 69 · 2012: 46
- FWCI
- 35.90
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion)
- PubMed Central (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Alzheimer's disease, amyloid-beta deposition, neurofibrillary tangles, neuritic plaques, ABC score, Lewy body disease, vascular brain injury, hippocampal sclerosis
- MeSH terms
- Alzheimer Disease, Brain, Cerebrovascular Disorders
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