Alzheimer’s Disease

Alzheimer’s disease (AD) is the most frequent neurodegenerative disease and the most common cause of senile dementia in humans. While AD affects multiple systems of the central nervous system (CNS), the classic and most frequent initial symptom is the loss of short-term memory that progresses to profound memory failure. As initially observed by Alzheimer, the brains of AD patients exhibit two hallmark neuropathological features: (1) senile plaques containing depositions of amyloid-β peptide (Aβ) and (2) neurofibrillary tangles (NFT) containing hyperphosphorylated microtubule-associated protein tau. Quantitative evaluation has revealed that in the early stages of AD, there is a significant loss of neurons in brain regions specifically involved in memory. Genetic studies have identified causative genes, amyloid precursor protein (APP), presenilin-1 (PSEN1), and presenilin-2 (PSEN2), which established that aberrant proteolytic processing of the APP leading to the formation of the Aβ 1-40 and 1-42 is primarily responsible for the pathogenesis of familial AD. However, the mechanisms by which APP processing leads to senile plaque deposition, NFT formation, and neuronal cell death remain elusive. The objective of this chapter is to review the current understanding of these mechanisms and the role played by neuroimmune interactions, primarily innate immunity in the CNS, in the disease process