Cited by 513Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsAmyotrophic Lateral Sclerosis Research

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Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia

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Mesulam, Marsel, Wicklund, Alissa, Johnson, Nancy, Rogalski, Emily, Léger, Gabriel C., Rademaker, Alfred, Weintraub, Sandra, Bigio, Eileen H.·2008·Annals of Neurology

DOI 10.1002/ana.21388PMC PMC2858311

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Abstract

Objective: To identify predictors of Alzheimer's disease (AD) versus frontotemporal lobar degeneration pathology in primary progressive aphasia (PPA), and determine whether the AD pathology is atypically distributed to fit the aphasic phenotype. Methods: Neuropsychological and neuropathological analyses of 23 consecutive PPA autopsies. All had qualitative determination of neurofibrillary tangle (NFT) density. Additional quantitation was done in four of the PPA/AD cases and four AD cases with the typical amnestic dementia of the Alzheimer type. Results: The sample contained mostly logopenic, agrammatic, and mixed forms of PPA. All six agrammatics had frontotemporal lobar degeneration (five of six with tauopathy). Seven of the 11 logopenics had AD. In logopenics, lower memory scores increased the probability of AD, but there were exceptions. The PPA/AD group showed predominance of entorhinal NFT typical of the amnestic dementia of the Alzheimer type. In the small subgroup examined quantitatively, neocortical NFTs were more numerous in the left hemisphere of PPA/AD. However, the asymmetry was low and inconsistent. Neuritic plaques did not display consistent asymmetry. Apolipoprotein E4, a major risk factor for typical AD, did not predict AD pathology in PPA. Interpretation: Subtyping PPA helps to predict AD versus frontotemporal lobar degeneration pathology at the group level. However, our results and the literature also indicate that no clinical predictor is completely reliable in individual patients. The inconsistent concordance of NFT distribution with the asymmetric atrophy and the nonamnestic phenotype also raises the possibility that the AD markers encountered at autopsy in PPA may not always reflect the nature of the initiating neurodegenerative process. Ann Neurol 2008

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Authors: Mesulam, M., Wicklund, A., Johnson, N., Rogalski, E., Léger, G. C., Rademaker, A., Weintraub, S., & Bigio, E. H.
Affiliations: Northwestern University (US)
Corresponding author: Mesulam, Marsel
ORCID: Mesulam, Marsel
Wicklund, Alissa
Johnson, Nancy
Rogalski, Emily
Léger, Gabriel C.
Rademaker, Alfred
Bigio, Eileen H.
Venue: Annals of Neurology
Publisher: Wiley
Published: 2008-04-15
Volume: 63
Issue: 6
Pages: 709-719
ISSN: 0364-5134 (ISSN-L)
1531-8249
DOI: 10.1002/ana.21388
PMC: PMC2858311
OpenAlex: W2135496343
Cited by: 513
References: 54
Citations by year: 2026: 16 · 2025: 14 · 2024: 18 · 2023: 14 · 2022: 18 · 2021: 23 · 2020: 28 · 2019: 28 · 2018: 32 · 2017: 29 · 2016: 24 · 2015: 31 · 2014: 31 · 2013: 54 · 2012: 43
FWCI: 25.77
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Annals of Neurology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institute on Aging (AG13854, P30AG013854)
National Institute on Deafness and Other Communication Disorders (R01DC008552, DC008552)
National Center for Research Resources (UL1RR025741)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords: primary progressive aphasia, Alzheimer's disease, frontotemporal lobar degeneration, neurofibrillary tangles, entorhinal cortex, logopenic aphasia, agrammatic aphasia, APOE ε4, neuritic plaques, hemispheric lateralization, neuropathology, differential diagnosis
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Dementia, Diagnosis, Differential, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Degeneration, Neurons, Phenotype, Biomarkers, Neurofibrillary Tangles, Disease Progression, Aphasia, Primary Progressive

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Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia

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