New research shows the proteins associated with Alzheimer’s disease and Parkinson’s disease interact to enhance each other’s distinct degenerative effects, indicating that therapies blocking the production or accumulation of either protein may have broader benefits than previously thought. The research is published in the September 25 Proceedings of the National Academy of Sciences.
Alzheimer’s disease and Parkinson’s disease are distinct neurological disorders, but up to one-third of Alzheimer’s patient develop Parkinson’s, and some Parkinson’s patient develop signs of Alzheimer’s.
To explore possible connections between the two diseases, scientists from UCSD’s departments of neurosciences and pathology, and from the Gladstone Institute of Neurological Diseases and the UCSF department of neurology, developed strains of transgenic mice that produce two human proteins, human amyloid precursor protein (hAPP) and human alpha-synuclein (hSYN), which are known to accumulate in Alzheimer’s and Parkinson’s, respectively.
Mice that produced one of the proteins developed the symptoms of the respective disease. But when both proteins were produced in the same mouse, the Alzheimer’s-like symptoms of the hAPP mice such as, degeneration of particular classes of brain cells and impaired learning ability, were exacerbated by the production of hSYN. The Parkinson-like motor deficits of the hSYN mice developed sooner in the mice that also expressed hAPP.
In addition, a metabolic breakdown product of hAPP, called Abeta, enhanced the accumulation of hSYN in brain cells, indicating a possible mechanism for the synergistic effects that were observed. Results of the study also clarify the underlying mechanisms that destroy the cognitive and motor functions of Alzheimer’s patients who also develop Parkinson’s.
The scientists speculate that because these proteins interact to accelerate and exacerbate the symptoms of their respective diseases, drugs aimed at preventing the accumulation of hAPP or hSYN could benefit a wider spectrum of neurodegenerative disorders than previously thought