A team of Stony Brook University researchers led by William Van Nostrand, PhD, Professor in the Department of Neurosurgery, has discovered in a model of Alzheimer’s disease that early accumulation of a small protein, known as amyloid β, in the blood vessels of the brain can drive early cognitive impairment. The findings, published in the current online edition of the Journal of Alzheimer’s Disease, suggest that targeting early buildup of amyloid in brain blood vessels could be a potential treatment strategy in early stage disease.
Alzheimer’s disease is a neurodegenerative condition that causes progressive decline in cognitive function. Studies have shown that in Alzheimer’s disease and related disorders there is an abnormal accumulation of amyloid in the brain that is believed by researchers to contribute to the dysfunction and eventual death of neuronal cells. When amyloid accumulates and aggregates in the Alzheimer’s disease process, amyloid deposits as either structures known as amyloid plaques around neuronal cells or deposits of amyloid in the blood vessels of the brain.
In the research paper, titled “Cerebral Microvascular Rather than Parenchymal Amyloid-β Protein Pathology Promotes Early Cognitive Impairment in Transgenic Mice,” the Stony Brook team compared two disease models – one that developed amyloid plaques and the other that developed cerebral blood vessel amyloid. The team assessed cognitive abilities at intervals and found that at three months, the model with brain blood vessel amyloid were cognitively impaired but the model with amyloid plaques were not cognitively impaired.
“Our results are intriguing because it appears cerebrovascular amyloid rather than amyloid plaques around neuronal cells is an early influence on cognitive decline,” said Dr. Van Nostrand. “This opens the door to continued investigation on the role of amyloid on brain blood vessels in the Alzheimer’s disease process and could be a first step toward developing more effective treatment targets for the onset of amyloid-associated cognitive impairment based on this particular type of amyloid buildup and associated pathologies.”
Interestingly, cognitive impairment in both models became similar at six months, which further suggests that the when amyloid continues to accumulate around neuronal cells and cerebral blood vessels cognitive impairment occurs.
Dr. Van Nostrand cautioned that much more investigation using various comparative amyloid models is necessary before concluding that cerebral blood vessel amyloid is a key treatment target for early disease onset. He added that while amyloid buildup appears to be a pathology associated with Alzheimer’s disease, given the complicated disease process, it is not fully known the relative impact of each of these amyloid lesions within the brain on cognitive impairment.
The work leading to the findings was supported in part by grants from the National Institutes of Health.
Co-authors on the paper include Dr. John K. Robinson, Maria E. Anderson, and Wen Jin Xu of the Department of Psychology at Stony Brook University; and Dr. Feng Xu, AnnMarie E. Kotarba, and Judianne Davis of the Departments of Neurosurgery and Medicine at Stony Brook University.
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“Cerebral Microvascular Rather than Parenchymal Amyloid-β Protein Pathology Promotes Early Cognitive Impairment in Transgenic Mice” by Wenjin Xu, Feng Xu, Maria E. Anderson, AnnMarie E. Kotarba, Judianne Davis, John K. Robinson, William E. Van Nostrand, Journal of Alzheimer’s Disease, Volume 38, Number 3, 2014, DOI 10.3233/JAD-130758. Published by IOS Press.