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Welcome to the Dickerson Lab: APOE gene effects on brain & cognition

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Since 1993, it has been known that the apolipoprotein E (APOE) gene has an important influence on the development of Alzheimer's disease (AD). If an individual carries one or two copies of the e4 version of the gene, they are at increased risk for AD. Not everyone with the APOE-e4 gene gets AD even if they live a long life, and many people with AD do not have the APOE-e4 gene--it is a risk factor. A great deal of effort has gone into understanding its biology, effects on the cellular and chemical pathology of AD, and related issues. It also may have some impact on response to treatment or side effects of possible treatments, although this is much less well understood.

Much less work has been done on whether the presence or absence of this gene may affect the ways AD presents itself clinically in patients with dementia or early symptoms of AD. There is evidence that patients with AD who carry the APOE-e4 gene may have worse memory function relative to patients with AD who do not have this gene, but it's been quite unclear whether there are greater impairments in "non-carriers" of this gene than carriers. Based on our clinical experience, Dr. David Wolk and I became interested in the observation that non-carriers may have worse executive function and possibly other cognitive functions.

We used the publicly available ADNI dataset to investigate this hypothesis, and discovered that it appears to be supported. That is, very mild and mild AD patients, who are in the earliest clinical stages of the illness, appear to be relatively better or worse at particular cognitive functions depending on their APOE genotype, and this relates to relatively lesser or greater abnormalities in the brain networks supporting these abilities. In particular, APOE-e4 carriers exhibit worse long-term memory performance and smaller medial temporal lobe brain regions than non-carriers. In contrast, APOE-e4 non-carriers exhibit relatively worse attention-executive and language functions, and greater atrophy in some brain regions supporting these functions, compared to carriers. Importantly, we showed that these results held when restricted to individuals whose cerebrospinal fluid protein profile (a-beta and tau) was consistent with AD.

The details of this work are described in the scientific paper in Proceedings of the National Academy of Sciences, and it received some media coverage as well.

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