Alzheimer's disease basics: we all should know.

Area of Science:

• Neuroscience
• Immunology
• Genetics

Background:

• Alzheimer's disease (AD) is a leading cause of dementia, impacting millions globally with progressive cognitive decline.
• Pathological hallmarks include amyloid-beta (Aβ) plaques, neurofibrillary tangles (NFTs) of tau protein, and chronic neuroinflammation.

Purpose of the Study:

• To review the molecular, genetic, and immunological factors contributing to Alzheimer's disease.
• To focus on pathogenic proteins, glial cell roles, and current monoclonal antibody (mAb) therapies.

Main Methods:

• Literature review of key players: Aβ, tau, microglia, and astrocytes.
• Analysis of genetic mutations (APP, PSEN1, PSEN2, APOE, BACE1, MAPT) and their impact.
• Review of clinical trial data for anti-Aβ mAbs (aducanumab, lecanemab, donanemab).

Main Results:

• Neuroinflammation exacerbates AD pathology, leading to synaptic loss and neuronal death.
• Monoclonal antibodies demonstrate potential in reducing Aβ burden and slowing cognitive decline (e.g., donanemab, lecanemab).
• Adverse events like ARIA are significant, especially in APOE-4 carriers; aducanumab was discontinued.

Conclusions:

• AD is multifactorial, involving protein aggregation, immune response, and genetic predisposition.
• mAb therapies offer disease modification potential but require precise patient stratification and safety monitoring.
• Future strategies necessitate personalized, combinatorial approaches integrating biomarkers and advanced technologies for AD management.