Risk factors for Alzheimer's disease

Area of Science:

• Neuroscience
• Genetics
• Epidemiology

Background:

• Over 20 risk factors for Alzheimer's disease (AD) have been identified, including age, genetics, and environmental exposures.
• Recent evidence prompts a re-evaluation of these risk factors and their etiological roles in AD.
• Familial and sporadic forms of AD have distinct underlying causes and risk factor profiles.

Purpose of the Study:

• To review and identify the most significant risk factors currently associated with Alzheimer's disease (AD).
• To discuss hypotheses explaining the mechanisms by which these risk factors contribute to AD pathology.
• To highlight the potential impact of lifestyle modifications on reducing AD risk.

Main Methods:

• Literature review of early and recent evidence on Alzheimer's disease (AD) risk factors.
• Analysis of genetic mutations linked to early-onset familial AD (EO-FAD).
• Examination of multifactorial risk factors implicated in late-onset sporadic AD (LO-SAD).

Main Results:

• Rare early-onset familial AD (EO-FAD) is strongly linked to mutations in APP and PSEN1/2 genes.
• Late-onset sporadic AD (LO-SAD) is multifactorial, involving age, Apo E, other genes, vascular disease, TBI, diet, immune function, and infections.
• Proposed mechanisms for AD pathology include oxidative stress, dual-hit hypothesis, and allostatic load.

Conclusions:

• Age, genetic predisposition, vascular factors, TBI, and infections are key risk factors for Alzheimer's disease (AD).
• Multiple interacting factors contribute to AD pathology through oxidative stress, environmental-gene interactions, or cumulative physiological burden.
• Lifestyle modifications targeting these risk factors may be crucial for lowering the incidence of Alzheimer's disease (AD).