Ginsberg Lab

Head of Lab

Stephen D. Ginsberg, PhD

The Vulnerability of Neuronal Cell Types to Brain Disease

The Ginsberg Lab, led by Stephen D. Ginsberg, PhD, aims to understand mechanisms underlying selective vulnerability associated with the Alzheimer’s disease (AD) spectrum. Our researchers extensively characterize individual populations of neurons from AD and Down syndrome (DS) models and postmortem brains from subjects diagnosed with no cognitive impairment (NCI), mild cognitive impairment (MCI), AD, or DS using high-throughput gene assays including laser capture microdissection paired with single population RNA sequencing (RNA-seq). We are studying individual ‘interactomes’ of vulnerable cell types and piecing them together into ‘connectomes’ which underlie memory and executive function decline seen in AD dementia with the intention of using these circuit maps to generate novel therapeutic approaches.

We are currently profiling selectively vulnerable neurons and comparing them to relatively spared neurons during AD onset and progression. Neuronal subtypes being profiled in animal models and postmortem human brains include basal forebrain cholinergic neurons, CA1 pyramidal neurons, and layer III and V frontal cortex pyramidal neurons. We are also analyzing selective vulnerability within the hippocampus by evaluating several different hippocampal neuron subtypes simultaneously. Parallel single population profiling studies are being performed in DS models and postmortem brains from individuals with DS, as they develop neuropathological changes associated with AD by early mid-life.

By understanding mechanisms driving the selective neuronal vulnerability and controlling these maladaptive responses may lead to the development of rational therapeutic approaches to abrogate dysfunction from interactomes to connectomes which are now being increasingly appreciated as endemic to neurodegenerative disorders. This design may provide a previously unavailable treatment approach to disorders, including AD, that are currently awaiting viable interventions.

Selected Publications

Alldred MJ, Penikalapati SC, Lee SH, Heguy A, Roussos P, Ginsberg SD. Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer's Disease. Mol Neurobiol. 2021 Oct;58(10):5141-5162. doi: 10.1007/s12035-021-02453-3. Epub 2021 Jul 14. PMID: 34263425
Click for abstract PDF

D'Acunzo P, Pérez-González R, Kim Y, Hargash T, Miller C, Alldred MJ, Erdjument-Bromage H, Penikalapati SC, Pawlik M, Saito M, Saito M, Ginsberg SD, Neubert TA, Goulbourne CN, Levy E. Mitovesicles are a novel population of extracellular vesicles of mitochondrial origin altered in Down syndrome. Sci Adv. 2021 Feb 12;7(7):eabe5085. doi: 10.1126/sciadv.abe5085. PMID: 33579698; PMCID: PMC7880603
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Gautier MK, Ginsberg SD. A method for quantification of vesicular compartments within cells using 3D reconstructed confocal z-stacks: Comparison of ImageJ and Imaris to count early endosomes within basal forebrain cholinergic neurons. J Neurosci Methods. 2021 Feb 15;350:109038. doi: 10.1016/j.jneumeth.2020.109038. Epub 2020 Dec 15. PMID: 33338543; PMCID: PMC8026492.


All publications

Ginsberg Lab Members

Melissa Alldred, PhD
Research Scientist
Amanda Labuza, PhD
Postdoctoral Researcher
Megan Gautier
Graduate Student
Harshitha Pidikiti
Research Technician
Arthur Saltzman
Research Technician