Review Article

Ocular Manifestations of Alzheimer’s Disease in Animal Models

Table 1

Hypotheses implicated in the development of Alzheimer’s disease.

Mechanisms implicated in ADPathophysiologyReferences

Amyloid hypothesisAggregation of Aβ peptides produces oligomers resulting in neurotoxicity and neuronal loss[1316]
Tau hypothesisHyperphosphorylation of tau proteins causes misfolding of microtubules, which leads to formation of NFT and disruption of the neuronal cytoskeleton[17, 18]
Cholinergic hypothesisLoss of cholinergic neurotransmission in the cerebral cortex. Oldest hypothesis on which current available treatments are based on[12]
Glutamatergic hypothesisThis hypothesis links AD to neuronal damage caused by overactivation of N-methyl-d-aspartate (NMDA) receptors by glutamate. It is suggested that low activation of NMDA receptor is essential for learning and memory[10]
Oxidative Stress hypothesisIn AD brains, Aβ generates reactive oxygen and nitrogen species which react with other molecules to form free radicals causing molecular and cellular damage Oxidative damage is thought to be early in AD progression because of its link with plaques and NFT.Oxidative stress by Aβ has been shown to be mediated by metal ions[7, 9, 19]
Chronic Inflammation hypothesisDuring AD, cytokines, reactive oxygen species, complement proteins, and prostaglandins are produced to cause chronic inflammation [11]