CHICAGO, June 11 (Xinhua) -- Researchers at Washington University School of Medicine in St. Louis have found that the types of brain cells damaged by Alzheimer's disease vary, and depend on the genes involved.
The findings were published June 8 in the journal Genome Medicine.
The researchers analyzed brain samples from deceased patients with rare and common forms of Alzheimer's. The tissue banks also included samples from people who did not have the disorder.
Using a computerized method, the researchers attempted to differentiate the effects of the genes and identify pathways that might be therapeutic targets.
They analyzed postmortem samples from the Mayo Clinic Brain Bank, the Mount Sinai Brain Bank and from the Knight Alzheimer's Disease Research Center at Washington University, as well as from deceased participants in the Dominantly Inherited Alzheimer Network (DIAN) Observational Study of people with genetic mutations that led to early-onset Alzheimer's.
Mutations in the genes APP, PSEN1 and PSEN2 are known to cause inherited Alzheimer's. Samples from such patients showed lower numbers of neurons and higher numbers of astrocytes than samples from people who had Alzheimer's but did not carry mutations in any of those genes.
The researchers found similar patterns of more astrocytes and fewer neurons in patients with APOE4, a gene known to increase the risk of late-onset Alzheimer' s. But in carriers of a gene variant called TREM2, neuronal loss was not as pronounced. Instead, the TREM2 mutation damaged glial cells in the brain.
Using computerized methods to identify what types of brain cells are present in tissue samples from deceased patients, the researchers also found that populations of various brain cell types are different, depending on which genes led to the development of Alzheimer's.
"Different genes contribute to Alzheimer's damage in different ways, and we are working to identify therapeutic targets to prevent that damage," said senior investigator Carlos Cruchaga, an associate professor of psychiatry at the university. "Alzheimer's always leads to neuronal death, but we might identify better targets for therapy if we know how various genes lead to damage."
