Acetyl-L-carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities.

Hyperhomocystinemia could induce tau protein hyperphosphorylation, β-amyloid (Aβ) accumulation, and memory deficits as seen in Alzheimer disease (AD), the most common cause of senile dementia with no effective cure currently. To search for possible treatment for AD, we produced a hyperhomocysteinemia model by vena caudalis injection of homocystine (Hcy) for 2 weeks and studied the effects of acetyl-L-carnitine (ALC) in rats. We found that simultaneous supplement of ALC could improve the Hcy-induced memory deficits remarkably, with attenuation of tau hyperphosphorylation and Aβ accumulation. Supplement of ALC almost abolished the Hcy-induced tau hyperphosphorylation at multiple AD-related sites. Supplementation of ALC also suppressed the phosphorylation of β-amyloid precursor proteins (APP), which may underlie the reduction of Aβ. Our data suggest that ALC could be a promising candidate for arresting Hcy-induced AD-like pathological and behavioral impairments.