What is it about?

Over the years there has been increasing recognition that Alzheimer’s disease (AD) includes many different non-amnestic clinical variants, now well known as Atypical AD. Our study specifically investigates two of these variants, the visual variant better known as Posterior cortical atrophy (PCA) and the language variant better known as Logopenic progressive aphasia (LPA). Apolipoprotein protein E (APOE) ε4 is a well-known important genetic risk factor for AD, but little is known about its influence in these atypical AD presentations. To better understand its effect, we enrolled a large cohort of 140 atypical AD patients who underwent magnetic resonance imaging and tau positron emission tomography and linear mixed effects models were used to compare cross-sectional and longitudinal regional metrics by APOE status.

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Why is it important?

In our study, we show that APOE ε4 predisposes the atypical AD presentations to greater medial temporal tau deposition and neurodegeneration, with evidence that medial temporal measures change faster, and hence start to catch up, in the APOE ε4 non-carriers. We believe that the genotype does play a role in the pathophysiology of the atypical AD variants and should be considered in future studies and clinical treatment trials.


APOE ε4 is important in atypical clinical presentations of AD and influences patterns of tau deposition and brain atrophy. Further research is needed to determine its influence on other clinical variants of atypical AD, such as dysexecutive AD, behavioral AD and corticobasal syndrome, to determine the generalizability of these findings.

Neha Atulkumar Singh
Mayo Clinic

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This page is a summary of: APOE ε4 influences medial temporal atrophy and tau deposition in atypical Alzheimer's disease, Alzheimer s & Dementia, June 2022, Wiley, DOI: 10.1002/alz.12711.
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