Tracking the earliest stages of neurodegenerative diseases, such as Alzheimer's, is proving to be one of the more important research challenges facing scientists today. A new review article from a team at the University of Southern California is suggesting leaks in the blood-brain barrier could be a useful early warning sign signaling the onset of everything from Parkinson's disease to multiple sclerosis before visible symptoms appear.
Almost every new drug target that's recently been developed to battle Alzheimer's and dementia has failed during its human clinical trial stages. While these disappointing results have led many scientists to abandon the classically held hypothesis underlying much current research, some think the key to battling dementia is catching it before major symptoms appear.
Unfortunately the big challenge is we simply don't currently have an effective or reliable way to catch diseases like Alzheimer's before major neurodegenerative symptoms appear. Everything from blood and eye tests to PET scans are being investigated in the rush to develop a reliable diagnostic tool that can catch these diseases early.
New work from scientists at USC is now suggesting signs of a breakdown in the blood-brain barrier – an almost impenetrable membrane that stops harmful particles from entering the brain – could be an effective precursor to many neurodegenerative diseases. The hypothesis is that when the blood-brain barrier becomes dysfunctional it potentially allows proteins such as beta-amyloid to move from other parts of the body – where it is generally harmless – into the brain, ultimately accumulating plaques considered to be fundamental to the pathology of cognitive decline.
"Cognitive impairment, and accumulation in the brain of the abnormal proteins amyloid and tau, are what we currently rely upon to diagnose Alzheimer's disease," says Berislav Zlokovic, one of the authors on the new article, "but blood-brain barrier breakdown and cerebral blood flow changes can be seen much earlier."
The new article suggests this breakdown in the blood-brain barrier can play an early role in the progression of Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and multiple sclerosis. It's also suggested that testing for leaks in the blood-brain barrier could offer an effective early-stage biomarker for many of these conditions.
A key issue is that tests for blood-brain barrier dysfunction are currently not significantly accessible, needing complex MRI or PET scans to identify signs of leakage. So while this hypothesis may not offer itself to be an especially useful diagnostic tool for treating regular patients, it may help researchers identify better subjects suited to early-stage medical trials designed to test new drugs that can slow or even stop the onset of neurodegenerative disease.
The new review article was published in the journal Nature Neuroscience.