Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia
Open accessAbstract
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
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2008-04-15
- Volume
- 63
- Issue
- 6
- Pages
- 709-719
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- 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
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › 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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