[Causative genes in Alzheimer's disease]

Area of Science:

• Neurogenetics
• Molecular Biology
• Gerontology

Context:

• Alzheimer's disease (AD) pathogenesis involves genetic factors, including amyloid precursor protein (APP), apolipoprotein E (apoE), and presenilin genes.
• While apoE genotype is linked to AD risk and progression, the genetic underpinnings of sporadic AD (SAD) remain incompletely understood.
• Estrogen receptor (ER) alpha gene polymorphisms represent a potential, yet under-explored, genetic risk factor for SAD.

Purpose:

• To investigate mutations in APP, PS-1, and PS-2 genes in familial Alzheimer's disease (FAD) cases.
• To examine the association between estrogen receptor (ER) alpha gene polymorphisms and sporadic Alzheimer's disease (SAD).
• To quantify apolipoprotein E (apoE) mRNA levels in the brains of AD and Down syndrome (DS) patients.

Summary:

• No mutations in APP, PS-1, or PS-2 genes were found in seven FAD cases.
• Significantly higher frequencies of P and X alleles of the ER alpha gene were observed in SAD patients compared to controls.
• ApoE mRNA levels were significantly elevated in the brains of both AD and DS patients relative to controls.

Impact:

• Estrogen receptor alpha gene polymorphisms may represent a novel genetic risk factor for sporadic Alzheimer's disease.
• Elevated apoE mRNA levels in AD and DS brains suggest a crucial role for apoE in the development of Alzheimer's pathology.
• Further research is needed to elucidate the precise mechanisms by which apoE influences AD development and progression.