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—degeneration of particular classes of brain cells, impaired ablity to learn—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.
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, the scientists speculate.
This work was conducted by Eliezer Masliah of UCSD, Lennart Mucke of the Gladstone Institute of Neurological Disease at UCSF, and Edward Rockenstein, Isaac Veinbergs, Yutaka Sagara, Margaret Mallory and Makoto Hashimoto of UCSD. The research was supported by the National Institutes of Health.
Laura Lane, Gladstone Institutes 415-695-3833
Proceedings of the National Academy of Sciences