A NEW UTMB STUDY HAS UNCOVERED WHY some people who have brain markers of Alzheimer’s disease never develop the classic dementia that others do. The study is now available in the Journal of Alzheimer’s Disease.
Alzheimer’s disease, the most common form of dementia, affects more than 5 million Americans. People suffering from Alzheimer’s develop a build-up of two proteins that impair communications between nerve cells in the brain—plaques made of amyloid beta proteins and tangles made of tau proteins.
Intriguingly to researchers, not all people with those signs of Alzheimer’s show cognitive decline during their lifetime. The question became, “What sets these people apart from those with the same plaques and tangles that develop the signature dementia?”
“In previous studies, we found that while the people without dementia but with Alzheimer’s neuropathology had amyloid plaques and neurofibrillary tangles just like those with dementia, the toxic amyloid beta and tau proteins did not accumulate at synapses, the point of communication between nerve cells,” said Giulio Taglialatela, director of the Mitchell Center for Neurodegenerative Diseases at UTMB.
“When nerve cells can’t communicate because of the build-up of these toxic proteins that disrupt synapses, thought and memory become impaired. The next key question was then ‘What makes the synapse of these resilient individuals capable of rejecting the dysfunctional binding of amyloid beta and tau?’”
To answer this question, researchers used high-throughput electrophoresis and mass spectrometry to analyze the protein composition of synapses isolated from frozen brain tissue donated by people who had participated in brain-aging studies and received annual neurological and neuropsychological evaluations during their lifetime.
The participants were divided into three groups: those with Alzheimer’s dementia, those with Alzheimer’s brain features but no signs of dementia and those without any evidence of Alzheimer’s.
The results showed that resilient individuals had a unique synaptic protein signature that set them apart from both AD patients with dementia and normal subjects with no AD pathology. Taglialatela said that this unique protein make-up may underscore the synaptic resistance to amyloid beta and tau, thus enabling these fortunate people to remain cognitively intact despite having Alzheimer’s-like pathologies.
“We don’t yet fully understand the exact mechanism responsible for this protection,” said Taglialatela. “Understanding such protective biological processes could reveal new targets for developing effective Alzheimer’s treatments.”
Other authors include UTMB’s Dr. Olga Zolochevska, Dr. Nicole Bjorklund, Dr. John Wiktorowicz and Dr. Randall Woltjer from Oregon Health and Science University.