Associate Professor, Baylor College of Medicine
B.S., Amherst College, MA, 1991
Ph.D., California Institute of Technology, 1999
Postdoc, Johns Hopkins School of Medicine, MD, 2000-03
Postdoc, California Institute of Technology, 2003-08
Functional consequences of Aβ accumulation in Alzheimer’s disease on hippocampal neurogenesis, synaptic plasticity, and cognitive behavior
The goal of our research is to understand how the abnormal accumulation of a small peptide known as Aβ leads to the overwhelming cognitive decline of Alzheimer’s disease. Implicit in our work is the idea that by understanding the relationship between Aβ and Alzheimer’s we will be able to design therapeutic strategies that disconnect their coupling to treat the disease. Our laboratory uses transgenic mice to explore how the presence of excess Aβ impacts the brain at levels ranging from individual neurons to complex behavior, using techniques of classic histology, electrophysiology, and cognitive testing. Current work focuses on a novel line of transgenic mice in which expression of the amyloid precursor protein, from which Aβ is derived, is controlled by a tetracycline-responsive promoter. This system allows us to study how the disease responds once the production of Aβ is blocked. Work so far has shown that this intervention stops the accumulation of Aβ into insoluble amyloid plaques, but that deposits formed prior to treatment will remain for life. Our goal now is to understand what level of functional recovery is possible while the pre-existing plaques remain in place, and whether a combination of therapies that remove residual aggregates will provide greater benefit.
A second avenue of research in the laboratory explores the role of individual cell populations and circuits in the cognitive decline of Alzheimer’s disease. Based on recent work in mouse models and decades of human neuropathology, we know which areas of the brain degenerate in Alzheimer’s patients, and relatively speaking, in what chronological order. Our goal is to understand how the sequential loss of these neuronal populations causes the progressive symptoms of Alzheimer’s. For this work we will develop transgenic mice expressing a chloride channel that selectively responds to a common anti-parasitic drug. On exposure to the drug, neurons expressing the channel become hyperpolarized, temporarily disengaging them from their normal circuit and reproducing how their loss would alter brain function in patients with Alzheimer’s disease. The first neuronal population we will target is in the hippocampus, an area critical for learning and memory, where we have shown that the survival of adult-born neurons is significantly reduced in mice overproducing Aβ. By its design, the silencer mouse will allow us to study the function of any population of neurons for which we can identify a specific promoter and an appropriate behavioral measure. Long-term, we will apply this strategy to other circuits affected in Alzheimer’s disease such as the basal forebrain cholinergic system and the entorhinal cortex, with the goal of elucidating how loss of each contributes to the disease.
Jankowsky JL, Slunt HH, Gonzales V, Jenkins NA, Copeland NG, Borchelt DR (2004) APP processing and amyloid deposition in mice haplo-insufficient for presenilin 1. Neurobiology of Aging 25:885-892.
Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG, Borchelt DR (2004) Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Human Molecular Genetics 13:159-170.
Jankowsky JL, Slunt HH, Gonzales V, Savonenko AV, Wen J, Jenkins NA, Copeland NG, Younkin LH, Lester HA, Younkin SG, Borchelt DR (2005) Persistent amyloidosis following suppression of Aβ production in a transgenic model of Alzheimer’s disease. PLoS Medicine 2:e355.
Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV (2005) Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer’s disease. Journal of Neuroscience 25:5217-5224.
Jankowsky JL, Younkin LH, Gonzales V, Fadale DJ, Slunt HH, Lester HA, Younkin SG, Borchelt DR (2007) Rodent ABeta modulates the solubility and distribution of amyloid deposits in transgenic mice. Journal of Biological Chemistry 282:22707-22720.
Verret L*, Jankowsky JL*, Xu G, Borchelt DR, Rampon C (2007) Alzheimer’s-type amyloidosis in mice impairs survival of newborn neurons derived from adult hippocampal neurogenesis. Journal of Neuroscience 27:6771-6780. (* equal contribution)
Badea A, Johnson GA, Jankowsky JL (2009) Automated volumetric MR analyses identify remote sites of structural atrophy prior to amyloid formation in a mouse model of Alzheimer’s disease. NeuroImage 50:416-427.
Wang A, Das P, Switzer RC, Golde TE, Jankowsky JL (2011) Robust amyloid clearance in a mouse model of AD provides novel insights into the mechanism of Aβ immunotherapy. Journal of Neuroscience 31:4124-4136.
Han HJ, Allen CC, Buchovecky CM, Yetman MJ, Born HA, Marin MA, Rodgers SP, Song BJ, Lu HC, Justice MJ, Probst FJ, Jankowsky JL (2012) Strain background influences neurotoxicity and behavioral abnormalities in mice expressing the tetracycline transactivator. Journal of Neuroscience 32:10574-10586.
Rodgers SP, Born HA, Das P, Jankowsky JL (2012) Transgenic APP expression during postnatal development causes persistent locomotor hyperactivity in the adult. Molecular Neurodegeneration 7:28.
Joanna L. Jankowsky, Ph.D.
Department of Neuroscience
Baylor College of Medicine
One Baylor Plaza 646E
Houston, Texas 77030, U.S.A.
Tel: (713) 798-8337
Fax: (713) 798-3946