Mormino Lab Research

Early Tau accumulation is detected within the medial temporal lobe using Tau PET imaging. 

RESEARCH OVERVIEW

Our overall research objective is to understand the risk of Alzheimer’s disease before clinical symptoms of dementia are present.  Alzheimer’s disease is a devastating neurodegenerative disorder that impacts over 5.5 million Americans, and there are currently no disease modifying treatments for this disease.  If this disease can be detected during the clinically silent stage, then we will be able to test preventative therapies before widespread neuronal damage has occurred.

To study the earliest stages of Alzheimer’s disease before any clinical symptoms are present, we take a multimodal approach to deeply phenotype our research volunteers.  Our studies integrate information from molecular PET imaging (especially Amyloid and Tau PET), MRI scans that provide information about brain structure and function, lumbar puncture to investigate the biomarkers in the cerebrospinal fluid, sensitive neuropsychological measurements, and genetics.  Our hope is that the combination of these data types will improve our ability to predict who is most at risk for dementia decades before clinical symptoms are present.  One of the primary complexities of understanding early Alzheimer’s disease is that there are numerous changes that occur during normal aging, and it is difficult to separate “pathological” versus “normal” aging.   By disentangling these changes we will improve our ability to predict risk of dementia at the individual person level, and understand the contributions of early Alzheimer’s disease processes in cognitive aging.

A critical tool in our work is Positron Emission Tomography (PET) imaging, which allows the visualization of specific targets in the brain. There have been a number of major advances in PET imaging related to Alzheimer’s disease.  In particular, we have the ability to measure the spatial distribution of the hallmark pathologies of Alzheimer’s disease—the accumulation of the amyloid and tau proteins.   Importantly, the aberrant accumulation of these proteins occurs years, if not decades, before clinical symptoms of dementia, allow us to investigate the early impact of these pathological insults.  We are currently investigating these PET scans in healthy older adults, as well as throughout the spectrum of impairment found in Alzheimer’s disease and other types of dementia.

In addition to examining early pathology with molecular imaging, we are interested in how genetic risk factors for Alzheimer’s Disease influence early changes that occur when individuals are asymptomatic.  Large genetic studies examining common genetic variants more prevalent in clinical dementia have provided clues into risk loci that may help with assessment of future risk among clinically asymptomatic individuals.  We are exploring the relationships between common genetic risk variants early Alzheimer’s Disease changes, especially with respect to subtle cognitive decline among clinically asymptomatic individuals.

Collaborators

Stanford

Anthony Wagner (Psychology)

Frederick Chin (Radiology)

Michelle James (Radiology and Neurology)

Greg Zaharchuk (Radiology)

Sharon Sha (Neurology)

Michael Greicius (Neurology)

Kathleen Poston (Neurology)

Carolyn Fredericks (Neurology)

Jacob Hall (Neurology)

Other Institutions

Reisa Sperling (Harvard)

Keith Johnson (Harvard)

Dorene Rentz (Harvard)

Kate Papp (Harvard)

Tian Ge (Harvard)

Yen Lim (University of Melbourne)

Mert Sabuncu (Cornell)

Thomas Yeo (National University of Singapore)

Research Resources