Summary
Alzheimer’s disease (AD) is a complex neurodegenerative condition significantly influenced by genetic factors, with the apolipoprotein E (ApoE) ε4 allele representing a prominent genetic risk factor. The ε4 isoform of ApoE is linked to increased amyloid-β peptide plaque formation and disruption of synaptic integrity, accelerating cognitive decline and neuronal dysfunction. ApoE also plays a critical role in lipid transport and metabolism, interacting with amyloid-β and tau proteins implicated in AD. The ε4 allele exacerbates these interactions, leading to increased plaque formation and tau aggregation compared to the more common ε3 allele. Conversely, the ApoE ε2 allele appears protective, reducing AD risk by altering amyloid-β dynamics. Ongoing therapeutic strategies are targeting ApoE to mitigate its effects, such as using antisense oligonucleotides, gene therapy approaches, or small molecules to alter ApoE expression and function. These efforts aim to clear amyloid-β more effectively and modulate lipid metabolism to preserve neuronal health. Understanding the distinct roles of each ApoE isoform helps in developing precision medicine strategies tailored to individual genetic profiles, offering insights into both potential prophylactic and therapeutic interventions for AD. Studies continue to explore the broader implications of ApoE in AD, including its interplay with lifestyle and environmental factors that might influence disease onset and progression.
Apolipoprotein E (APOE) genotype is linked to Alzheimer's risk and cognitive decline. APOE4 allele affects amyloid deposition and neural inflammation.
Published By:
CC Liu, T Kanekiyo, H Xu, G Bu - Nature Reviews Neurology, 2013 - nature.com
APOE's impact on Alzheimer's includes pathways influencing amyloid, tau, and neuroinflammation. Therapeutic strategies targeting APOE vary, focusing on reducing apoE levels, structural correctors, and lipid modulating techniques.
Published By:
AC Raulin, SV Doss, ZA Trottier, TC Ikezu, G Bu… - Molecular …, 2022 - Springer
ApoE4 is a crucial genetic risk factor for Alzheimer's disease, influencing Aβ metabolism and tau phosphorylation. Recent studies emphasize its potential as a therapeutic target, suggesting new treatments and interventions for ApoE4 carriers.
Published By:
M Safieh, AD Korczyn, DM Michaelson - BMC medicine, 2019 - Springer
ApoE4, a gene linked to Alzheimer's, causes mitochondrial dysfunction and gene regulation issues. Therapeutic strategies include increasing ApoE2, reducing ApoE4, and targeting lipid metabolism.
Published By:
M Pires, AC Rego - International Journal of Molecular Sciences, 2023 - mdpi.com
APOE gene variants influence Alzheimer's risk through amyloid and lipid mechanisms. Targeting APOE may offer preventive strategies for Alzheimer's and age-related dementias.
Published By:
G Bu - Molecular neurodegeneration, 2022 - Springer
Seven of eight major payers don't cover ApoE testing for AD due to insufficient clinical utility. Future advancements in treatment may prompt a reevaluation of coverage policies.
Published By:
JJ Arias, AM Tyler, MP Douglas, KA Phillips - Genetics in Medicine, 2021 - Elsevier
APOE-ɛ4 affects gray matter volume in key brain regions related to Alzheimer's risk. It may indicate structural brain changes in healthy individuals, correlating with possible disease vulnerability.
Published By:
R Cacciaglia, JL Molinuevo, C Falcón… - Alzheimer's & …, 2018 - Elsevier
APOE alleles influence Alzheimer's risk with lifestyle and environment. Preventive measures may help.
Published By:
E Angelopoulou, YN Paudel… - ACS chemical …, 2021 - ACS Publications
Studies explore genetic risk, perception, and testing for Alzheimer's, highlighting APOE's role. Research also examines communication, behavior, and ethical issues in genetic testing.
Published By:
VS Marshe, I Gorbovskaya, S Kanji, M Kish… - Journal of Neural …, 2019 - Springer
Alzheimer's incidence varies significantly by ethnicity in APOE ∊3/∊3 genotype, controlled for education. African Americans and Hispanics show higher risks than whites.
Published By:
MX Tang, Y Stern, K Marder, K Bell, B Gurland… - Jama, 1998 - jamanetwork.com