Alzheimer’s Disease

Brains from Alzheimer's patient (left) and normal patient (right)
Alzheimer's brain (left) versus normal brain (right). UCSF image.

We are using a unique transgenic rat model of Alzheimer's disease to investigate a number of questions:

  • Is traffic-related air pollution (TRAP) an environmental risk factor for AD? If so, what component(s) in TRAP increase risk for AD phenotypes and how? (Collaborators: Tony Wexler, Keith Bein, Jill Silverman, Laura Van Winkle, Fred Gorin)
  • What is the influence of diet on the rate of onset or symptom severity of AD? (Collaborators: Ameer Taha and Jon Ramsey)
  • What is the role of senescent endothelial cells and neuroinflammation in the pathogenesis of AD? (Collaborators: Anne Knowlton, Angie Gelli, Fred Gorin)
  • Are PET tracers that label synapses or neuroinflammation more predictive of early stages of AD than PET tracers for amyloid plaques and neurofibrillary tangles? (Collaborator: Abhijit Chaudhari)

Current funding:
Vascular Inflammation and Exosomes as Mediators in Aging and Dementia
NIH/NIA R01 AG056710 (Knowlton/Lein/Gelli) 04/01/18 - 03/31/23
The goal of this project is to test the hypothesis that senescent endothelial cells, which accumulate with aging, create a pro-inflammatory environment that adversely affects the blood brain barrier (BBB) and contribute to neuropathology implicated in age-associated dementias such as Alzheimer’s disease.

Imaging Biomarkers of Early Synaptic Changes in a Preclinical Model of Alzheimer’s disease
R21 AG064599 Chaudhari (Contact) and Lein (MPI) 07/01/2019 – 06/30/2021
The goal is to test the hypothesis that in vivo imaging of synapse density is a predictive biomarker of AD pathology that precedes detection of amyloid deposition and neurofibrillary tangles by in vivo imaging.