APOE-amyloid interaction: Therapeutic targets

NEUROBIOLOGY OF DISEASE

卷:138

Review

Wisniewski, Thomas^1,2,3  Drummond, Eleanor^4,5 

[1] NYU, Sch Med, Ctr Cognit Neurol, Dept Neurol, Sci Bldg Km 1017,435 East 30th St, New York, NY 10016 USA

[2] NYU, Sch Med, Ctr Cognit Neurol, Dept Pathol, Sci Bldg Km 1017,435 East 30th St, New York, NY 10016 USA

[3] NYU, Sch Med, Ctr Cognit Neurol, Dept Psychiat, Sci Bldg Km 1017,435 East 30th St, New York, NY 10016 USA

[4] Univ Sydney, Fac Med & Hlth, Brain & Mind Ctr, Sydney, NSW, Australia

[5] Univ Sydney, Fac Med & Hlth, Cent Clin Sch, Sydney, NSW, Australia

关键词: Apolipoprotein E;    Immunomodulation;    Oligomers;    Early onset AD;    Therapy;    Peptoids;    Pathological chaperone;    Beta amyloid;    Interaction;   

DOI  :  10.1016/j.nbd.2020.104784

来源: Elsevier

【 摘 要 】

Alzheimer's disease (AD) is a devastating neurodegenerative disorder that is growing in prevalence globally. It is the only major cause of death without any effective pharmacological means to treat or slow progression. Inheritance of the epsilon 4 allele of the Apolipoprotein (APO) E gene is the strongest genetic risk factor for late-onset AD. The interaction between APOE and amyloid beta (A beta) plays a key role in AD pathogenesis. The APOE-A beta interaction regulates A beta aggregation and clearance and therefore directly influences the development of amyloid plaques, congophilic amyloid angiopathy and subsequent tau related pathology. Relatively few AD therapeutic approaches have directly targeted the APOE-A beta interaction thus far. Here we review the critical role of APOE in the pathogenesis of AD and some of the most promising therapeutic approaches that focus on the APOE-A beta interaction.