Principal Investigators: Philip Wong, Ph.D., and Tong Li, Ph.D.

The goal of this project is to characterize a recently developed mouse model that not only exhibits amyloid β (Aβ) amyloidosis and tauopathy, but also displays robust age-dependent neuronal loss. This new mouse model will be used to test the overarching hypothesis that Aβ induces tau aggregation, which in turn initiates synaptic dysfunction and promotes neuronal loss. The research team hopes is that such a model system will provide the opportunity to evaluate Aβ amyloidosis and tauopathy dependent loss of neurons as the principal outcome measure in preclinical testing of mechanism-based therapies, such as those designed to target tauopathy and/or Aβ amyloidosis.

For more information, contact Dr. Philip Wong at pwong@jhmi.edu.

Principal Investigator: Alena Savonenko M.D., Ph.D.

Transgenic mouse models of amyloidosis can be used to examine the impact of treatment associated with varying levels of amyloid deposition. This project uses TetOffAPP mice in which the expression of mutant amyloid precursor protein (APP) is controlled by a tetracycline-regulated promoter. A-beta production can be suppressed in these mice with doxycycline. The goal of this project is: (1) To determine if the cognitive impairments observed in these mouse models be reversed with suppression of A-beta generation. (2) To determine whether recovery of synaptic damage is associated with cognitive improvement after A-beta production is reduced. (3) Aim 3: To examine the role of monoamine systems in relation to the degree of cognitive recovery observed after reduction of A-beta production. Collectively, outcomes from these studies will address an important issue regarding the value of an anti-amyloid therapeutic strategy for AD by assessing the magnitude of functional repair and recovery after synaptic damage by A-beta.

For more information, contact Alena Savonenko at asavone1@jhmi.edu.

Principal Investigator: Joseph Coresh, M.D.

The goal of this study is to determine if late-life cognitive impairment and dementia are associated with midlife vascular risk factors. This is a multidisciplinary, multi-center prospective study of 15,792 black and white, men and women, who were aged 45-64 when they were first examined in 1987. The study emphasizes the impact of mid-life vascular risks on subsequent mild cognitive impairment (MCI) and dementia because of the potential that risk-modification may lower the prevalence of MCI or dementia in late life.

For more information, contact Joseph Coresh at jcoresh1@jhmi.edu.

Principal Investigator: Marilyn S. Albert, Ph.D.

The goal of this study is to identify predictors of cognitive decline among normal individuals. The domains of investigation being examined include: clinical and cognitive assessments, magnetic resonance imaging, amyloid imaging, cerebrospinal fluid and blood. The primary question is whether measures from these domains, alone or in combination, obtained when participants are middle-aged, can predict which normal individuals will develop cognitive decline over time.

For more information, contact Marilyn Albert at malbert9@jhmi.edu.

Principal Investigator: Peter van Zijl, Ph.D.

The goal of this study is to determine if it is possible to see amyloid plaques in the brains of patients with Alzheimer’s disease, using a 7 tesla magnetic resonance imaging scanner. It is hypothesized that this high field strength will make it possible to image amyloid plaques because of magnetic susceptibility effects caused by the presence of iron in the plaques.

For more information, contact Sydney Feagen at sfeagen1@jhmi.edu.