Reduced
glucose metabolism is an invariant feature of
Alzheimer's Disease (AD) and an outstanding
biomarker of
disease progression.
Glucose metabolism may be an attractive therapeutic target, whether the decline initiates AD pathophysiology or is a critical component of a cascade. The cause of cerebral regional
glucose hypometabolism remains unclear.
Thiamine-dependent processes are critical in
glucose metabolism and are diminished in brains of AD patients at autopsy. Further, the reductions in
thiamine-dependent processes are highly correlated to the decline in clinical dementia rating scales. In animal models,
thiamine deficiency exacerbates plaque formation, promotes phosphorylation of tau and impairs memory. In contrast, treatment of mouse models of AD with the
thiamine derivative
benfotiamine diminishes plaques, decreases phosphorylation of tau and reverses
memory deficits. Diabetes predisposes to AD, which suggests they may share some common mechanisms.
Benfotiamine diminishes
peripheral neuropathy in diabetic humans and animals. In diabetes,
benfotiamine induces key
thiamine-dependent
enzymes of the pentose shunt to reduce accumulation of toxic metabolites including
advanced glycation end products (AGE). Related mechanisms may lead to reversal of plaque formation by
benfotiamine in animals. If so, the use of
benfotiamine could provide a safe intervention to reverse
biological and clinical processes of AD progression. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.