Advanced histological techniques for the study of Alzheimer’s disease pathophysiology.

 Alzheimer’s disease is the most common dementia in the elderly, affecting more than 5 million Americans. Pathologically, the Alzheimer’s disease brain is characterized by the deposition of the amyloid beta peptide in extracellular amyloid plaques and of the microtubule-associated protein tau in intraneuronal neurofibrillary tangles, together with severe loss of neurons resulting in brain atrophy. But, besides plaques, tangles, and atrophy, there is a prominent reaction of glial cells - astrocytes and microglia - which is gaining attention from the research community. The role of these glial responses in the pathophysiology of the disease remains uncertain, but some recent studies support a detrimental effect through either a gain of toxic function or a loss of neurotrophic support.

My aim is to improve our understanding of the astrocyte and microglial responses in the Alzheimer’s disease brain by using advanced histological techniques on brain specimens from Alzheimer’s disease patients and age-matched healthy control subjects. Specifically, I have learned and implemented two methods that are enabling us to phenotype glial cells in situ in a high-throughput quantitative fashion: multiplex immunohistochemistry and array tomography.

In this seminar, I will discuss the basis and troubleshooting of these two methods, and highlight their applications for the study of Alzheimer’s disease.

Speaker: Clara Muñoz Castro, Visiting Researcher at Massachusetts General Hospital (Alzheimer’s Disease Research Unit), Harvard Medical School