Abstract
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the most common cause of dementia in the elderly people. Amyloid beta 42 peptide (Aβ42) is the primary constituent of amyloid plaques, a major pathological hallmark of AD. It is well known that the dysfunction in both cholinergic and glutamatergic systems contribute to the symptomatology of AD, but the exact causes remain unclear. Here, we use Drosophila as a model system to examine the effects of overexpression of the human Aβ42 peptides on the populations of glutamatergic and cholinergic neurons. The expression of Aβ42 resulted in an initially increased glutamate neurotransmission, and subsequently Aβ42 led to an age-dependent progressive degeneration of neurons. The neurodegeneration was accompanied by defects in locomotion activity and decreased longevity. Similarly, flies overexpressing Aβ42 in cholinergic neurons cause an age-dependent neurodegeneration, and shortened lifespan. Moreover, we found that there may be an interaction between Aβ42 and wild-type tau protein. Taken together, our flies may serve as an early-onset model to understand molecular mechanisms underlying Aβ toxicity and to discover the new therapeutic targets for AD.