This open access paper is illustrative of present work on the role of microglial dysfunction and chronic inflammation in Alzheimer’s disease. The central nervous system immune cells called microglia become inappropriately inflammatory with age. A new consensus on Alzheimer’s disease is that initial amyloid-β accumulation causes far greater than usual chronic disarray and inflammatory signaling in the supporting cells of the brain, such as microglia, astrocytes, and oligodendrocytes. This in turn leads to the much more damaging tau aggregation and consequent damage and death of neurons.
Alzheimer’s disease (AD) is characterized by typical biochemical lesions (β-amyloid peptide [Aβ] plaques and tau tangles) accompanied by extensive cellular changes (neuronal dystrophic alterations, neuronal cell loss, astrogliosis, and microgliosis). Rare mutations in amyloid precursor protein (APP), presenilin 1 and presenilin 2 trigger Aβ plaque accumulation and are sufficient to induce the full biochemical and morphological signature of AD. While this clearly indicates a major role for Aβ in AD pathology even in these genetic forms, a decades-long asymptomatic phase is present. Thus, in addition to Aβ plaques, other pathological processes, either in response to or in parallel to Aβ accumulation, need activation to cause neurodegenerative disease.