Unraveling how neuronal “traffic jams” develop within the brain could be key to scientists’ understanding of diseases like Alzheimer’s.
Researchers at the State University of New York (SUNY) at Buffalo, Carnegie Mellon University, and the University of California, San Diego (UCSD), have found that perturbations of amyloid precursor protein and presenilin transport may be partly to blame.
Writing in Human Molecular Genetics, UCSD’s Lawrence Goldstein, Ph.D., and his colleagues show that axonal transport defects induced by the loss of presenilin-mediated regulatory effects on amyloid precursor protein vesicle motility could be a major cause of the neuronal and synaptic issues associated with Alzheimer’s disease pathogenesis.
Further, Dr. Goldstein et al., suggest these amyloid precursor protein and presenilin perturbations may contribute to the early Alzheimer’s neuropathology, and point to a potential therapeutic pathway for intervention prior to neuronal loss.
“Our major discovery is that presenilin has a novel role, which is to control the movement of motor proteins along neuronal highways,” study co-author Shermali Gunawardena, Ph.D., from SUNY Buffalo said in a statement. “If this regulation/control is lost, then things can go wrong. …In Alzheimer’s disease, transport defects occur well before symptoms, such as cell death and amyloid plaques, are seen in post-mortem brains.”
Thus, Dr. Gunawardena added: “Developing therapeutics targeted to defects in neuronal transport would be a useful way to attack the problem early.”
The study, “Presenilin controls kinesin-1 and dynein function during APP vesicle transport in vivo,” was published May 24 in Human Molecular Genetics.