A recent study at the National Institute on Aging discovered proteins and biological processes that could help develop new treatment of Alzheimer’s disease.
It showed that proteins that regulate blood sugar metabolism, together with proteins related to a protective role of astrocytes and microglia—the brain’s support cells—are strongly linked to Alzheimer’s disease and cognitive impairment.
The study is published in Nature Medicine. One author is NIA Director Richard J. Hodes, M.D.
The team tested the levels and analyzing the expression patterns of more than 3,000 proteins in a large number of brain and cerebrospinal fluid samples collected at multiple research centers across the United States.
They analyzed patterns of protein expression in more than 2,000 human brains and nearly 400 cerebrospinal fluid samples from both healthy people and those with Alzheimer’s disease.
The researchers then analyzed how the protein modules relate to various pathologic and clinical features of Alzheimer’s and other neurodegenerative disorders.
They saw changes in proteins related to glucose metabolism and anti-inflammatory response in glial cells in brain samples from both people with Alzheimer’s as well as in samples from people with brain pathology who were cognitively normal.
This suggests that the anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease.
The researchers also set out to reproduce the findings in cerebrospinal fluid.
They found that, just like with brain tissue, the proteins involved in the way cells extract energy from glucose are increased in the spinal fluid from people with Alzheimer’s.
Many of these proteins were also elevated in people with preclinical Alzheimer’s, i.e., individuals with brain pathology but without symptoms of cognitive decline.
Importantly, the glucose metabolism/glial protein module was populated with proteins known to be genetic risk factors for Alzheimer’s, suggesting that the biological processes reflected by these protein families are involved in the actual disease process.
The analysis shows that these proteins may also have potential as biomarkers to detect the presence of early Alzheimer’s disease.
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