I am interested in human aging and Alzheimer’s disease.  My research is motivated by the following questions:

How does pathology impact the aging brain?
How are some individuals able to remain cognitively normal despite substantial pathology?

To address these questions, I have employed a multi-modal neuroimaging approach to study the aging brain. Recent advents in neuroimaging enable many facets of the brain to be explored in living humans: PIB-positron emission tomography (PET) imaging provides a measure of beta-amyloid (Aβ) plaque burden (a pathology thought to cause Alzheimer’s disease), functional magnetic imaging (fMRI) provides measures of brain activation during cognitive tasks, and structural MRI provides measures of neuronal loss.  By combining these neuroimaging techniques, we can begin to understand the intricate relationships between underlying brain pathology and changes that occur in brain function and structure.

Although Aβ is thought to cause Alzheimer’s disease, this pathology is present in many clinically normal elderly individuals.

Click here for figure details.

There are many explanations for the presence of Aβ plaques in clinically normal individuals:

1) The amyloid hypothesis is incorrect (or too simplistic).

2) Elderly individuals with high amounts of Aβ are in the earliest stage of Alzheimer’s disease (“preclinical AD”), and will eventually progress to Alzheimer’s disease dementia.

3) Some individuals are able to cope with high levels of Aβ while others are not (due to genetics, an ability to elicit compensatory neuronal mechanisms, a lower incidence of other age-related pathologies, etc etc etc).

4) Aβ plaques are protective whereas soluble oligomeric species are the damaging form of Aβ (which are difficult to measure).

I believe the answer is a combination of explanations 2 and 3….but we should let the data decide (research investigating the relevance of Aβ in living humans is still in it’s infancy)!

Importantly, understanding the impact of Aβ will elucidate mechanisms underlying some of the neuronal and cognitive changes observed in human aging.  These relationships may offer insight into Alzheimer’s disease development, and potentially reveal an ideal window for preventing Alzheimer’s disease dementia in high risk clinically normal individuals.

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