Another Cause of Alzheimers
In 1906, a psychiatrist, Alois Alzheimer described to a group of German physicians a peculiar patient he had been treating. The woman developed paranoia that progressed quickly, and that was the first description of what we now call Alzheimer’s disease or AD, aptly named after him. After she died, Alzheimer did an autopsy and found abnormal patterns we now know as plaques and neurofibrillary tangles that may contribute to AD.
Another feature of her brain was fat droplet accumulation within glial cells, which support and protect neurons. Researchers are now studying this fat droplet because treatments on plaques and tangles haven’t worked well. Scientists already know that some variants of a gene for proteins involved in the transport of fats are risk factors for AD. They’re linked to greater fat deposits in the glial cells and in mouse studies that led to cell dysfunction.
A new study worked with human AD brain cells and one of the gene variants. When neurons in a Petrie dish were treated with media from glial cells that contain the fat droplets, it seemed to be toxic to the tau protein that causes the tangles seen in Alzheimer’s.
Now scientists wonder whether the protein that produces plaque in the brain induces fat droplet accumulation in glial cells. The glial cells then produce a secretion that’s toxic to neurons causing them to degenerate. Targeting this process might help scientists make more headway into Alzheimer’s, which affects millions of people while treatments have mostly stalled.
More Information
APOE4/4 is linked to damaging lipid droplets in Alzheimer’s disease microglia
Several genetic risk factors for Alzheimer’s disease implicate genes involved in lipid metabolism and many of these lipid genes are highly expressed in glial cells1. However, the relationship between lipid metabolism in glia and Alzheimer’s disease pathology remains poorly understood. Through single-nucleus RNA sequencing of brain tissue in Alzheimer’s disease, we have identified a microglial state defined by the expression of the lipid droplet-associated enzyme ACSL1 with ACSL1-positive microglia being most abundant in patients with Alzheimer’s disease having the APOE4/4 genotype.
The Hidden Cause of Alzheimer's May Have Been Identified a Century Ago
Alzheimer's disease is commonly associated with clumps and tangles of proteins building up in brain cells. Yet for more than a century, accumulations of a completely different material have also been linked with the neurodegenerative condition. A study led by researchers from the Stanford University School of Medicine returned to observations of large fat drops made by Alois Alzheimer when he made critical descriptions of the pathology at the turn of the 20th century.
Alzheimer’s Disease: Past, Present, and Future
Although dementia has been described in ancient texts over many centuries (e.g., “Be kind to your father, even if his mind fail him.” – Old Testament: Sirach 3:12), our knowledge of its underlying causes is little more than a century old. Alzheimer published his now famous case study only 110 years ago, and our modern understanding of the disease that bears his name, and its neuropsychological consequences, really only began to accelerate in the 1980s. Since then we have witnessed an explosion of basic and translational research into the causes, characterizations, and possible treatments for Alzheimer’s disease (AD) and other dementias.