Robert
James Vassar, PhD
Associate Professor
Dept. of Cell and Molecular Biology
To contact Dr. Vassar:
Phone: 312-503-3361
E-mail: r-vassar@northwestern.edu
Dr. Vassar's website
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Research Interests
Alzheimer’s disease (AD) is the leading cause of dementia in the elderly.
The progressive degeneration of neurons in regions of the brain important
for cognition causes the dementia that slowly robs AD patients of their memories,
personalities, and eventually their lives. No therapies currently exist that
treat the underlying pathology of AD, and if none are found, the number of
AD patients is projected to rise dramatically due to the aging of the population.
Clearly, the need for AD treatments is great, and understanding the pathophysiological
mechanisms that underlie neurodegeneration in AD is essential for rational
design of therapies.
AD pathology is characterized
by two microscopic brain lesions, amyloid plaques and neurofibrillary tangles.
Amyloid plaques are extracellular deposits of the beta-amyloid peptide (Ab),
and the longer 42 amino acid form, Ab42, is strongly associated with autosomal
dominant forms of familial AD suggesting that Ab42 has a critical and early
role in AD pathogenesis. Ab is generated from the amyloid precursor protein
(APP) by endoproteolysis from two proteases called the b- and g-secretases.
The b-secretase, a novel aspartic protease termed BACE1, was initially cloned
and characterized by our group (Vassar, et al., 1999). BACE1 is required for
the generation of all forms of Ab, including Ab42, and therefore is a prime
drug target for the treatment of AD. We have recently generated BACE1 knockout
mice by gene targeting and have validated BACE1 as the authentic b-secretase
in vivo (Luo et al., 2001). Importantly, BACE1 knockout mice have a normal
phenotype, suggesting that therapeutic inhibition of BACE1 for AD may be free
of mechanism-based toxicity. Although BACE1 is clearly a key enzyme required
for the processing of APP into Ab, other potential substrates and functions
of BACE1 are unknown.
Dr. Robert Vassar’s ongoing research focuses on the role of Ab and BACE1 in normal biological processes and in disease mechanisms of relevance to AD. His laboratory is particularly interested in the functions of BACE1 and the homologue, BACE2, and the cell biology of Ab in neurons. Cellular and molecular studies of BACE1 and BACE2 knockout mice will be important for elucidating the biological functions of these novel aspartic proteases and identifying their substrates. His lab is also interested in the role of inflammation in AD pathophysiology, novel transgenic and knockout mouse models of AD, and molecular changes that may occur during brain aging leading to neurodegeneration.