Bret Stetka, MD; José G. Merino, MD, MPhil


April 24, 2013

Two Exciting Finds in Alzheimer Disease

Medscape: Very interesting. The other 2 talks also focused on dementia. Can you tell us about these presentations?

Dr. Merino: John Q. Trojanowski, MD, PhD, a professor of geriatric medicine at the University of Pennsylvania, talked about his work on cell-to-cell spread of pathological tau. He has been working on the transmission of tau fibrils along neurons in rodent models. His work has significant implications in terms of not only how Alzheimer disease (AD) and other tauopathies develop and affect different areas of the brain but also may one day lead to preventive strategies.

In his talk, Dr. Trojanowski described recent work in which his team injected preformed fibrils made from synthetic tau into the cortex of transgenic mice and found that these particles induced the formation of tau inclusions that were immunochemically similar to AD tangles in areas of the brain connected to the area of injection. This was the first report that synthetic tau could induce the spread of AD pathology. The findings confirm that abnormal protein aggregates can move from cell to cell, and that preformed fibrils can initiate the process.

Medscape: Similar work is also under way in Parkinson disease, correct?

Dr. Merino: Yes. We're seeing similar findings with alpha-synuclein in Parkinson disease. It is possible that this mechanism of abnormal protein induction and transmission may be implicated in several neurodegenerative conditions that are characterized by accumulation of abnormal proteins.

Dr. Alison Goate, from Washington University, gave the fourth excellent talk. She is a pioneer in the field of Alzheimer genetics, as she reported the first genetic mutation that causes early-onset AD and was part of the teams that discovered genes that cause frontotemporal dementia and amyotrophic lateral sclerosis.

In her talk, Dr. Goate described current work using genome-wide association studies (GWAS) to identify genes involved in late-onset AD (LOAD). Several groups and collaborations have used this approach to identify several gene variants that increase the risk for LOAD. Some of these studies have found that genes associated with early-onset AD may also play a role in LOAD (but have lower penetrance). But with GWAS, new genes that increase risk for LOAD are being identified. Recently, for example, a collaboration of several centers found that a new gene variant, TREM2, increased the risk for AD by 2- to 4-fold, about the same as being an ApoE4 carrier.

These talks highlight the exciting state of the field of neurology today.