The impact of luteinizing hormone and testosterone on beta amyloid (Aβ) accumulation: Animal and human clinical studies

Giuseppe Verdile; Prita R Asih; Anna M Barron; Eka J Wahjoepramono; Lars M Ittner; Ralph N Martins

doi:10.1016/j.yhbeh.2015.05.020

The impact of luteinizing hormone and testosterone on beta amyloid (Aβ) accumulation: Animal and human clinical studies

Horm Behav. 2015 Nov:76:81-90. doi: 10.1016/j.yhbeh.2015.05.020. Epub 2015 Jun 27.

Authors

Giuseppe Verdile¹, Prita R Asih², Anna M Barron³, Eka J Wahjoepramono⁴, Lars M Ittner⁵, Ralph N Martins⁶

Affiliations

¹ School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Bentley, Western Australia 6102, Australia; Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia. Electronic address: Giuseppe.verdile@curtin.edu.au.
² Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of NSW, Kensington, NSW 2052, Australia.
³ National Institute of Radiological Sciences, Chiba-shi, Chiba 263-8555, Japan.
⁴ Sir James McCusker Alzheimer's disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia; Medical Faculty, Pelita Harapan University - Neuroscience Centre, Siloam Hospital, Lippo Karawaci, Tangerang, Indonesia.
⁵ Dementia Research Unit, Department of Anatomy, School of Medical Sciences, Faculty of Medicine, University of NSW, Kensington, NSW 2052, Australia; Neuroscience Research Australia, Randwick, NSW 2036, Australia.
⁶ Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University, Joondalup, Western Australia 6027, Australia; Sir James McCusker Alzheimer's disease Research Unit, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Western Australia 6009, Australia; School of Biomedical Sciences, CHIRI Biosciences, Curtin University, Bentley, Western Australia 6102, Australia.

PMID: 26122291
DOI: 10.1016/j.yhbeh.2015.05.020

Abstract

This article is part of a Special Issue "SBN 2014". Hormonal changes associated with ageing have been implicated in the pathogenesis of Alzheimer's disease (AD), the most common form of dementia. Reductions in serum testosterone and increases in luteinizing hormone (LH) are established AD risk factors for dementia in men and have important roles in modulating AD pathogenesis. One of the defining features of AD is the accumulation of amyloid-beta (Aβ) in the brain, which has a key role in the neurodegenerative cascade. Both testosterone and LH have been shown to modulate CNS Aβ accumulation in animal studies, and associations with cerebral amyloid load in human studies have supported this. The underlying mechanisms by which these hormones modulate Aβ accumulation and contribute to neurodegeneration are not completely understood, however they have been shown to regulate Aβ metabolism, enhance its clearance and alter the processing of its parent molecule, the amyloid precursor protein. This review will discuss underlying mechanisms by which testosterone and LH modulate Aβ and provide an update on therapeutic approaches targeting these hormones.

Keywords: Alzheimer's disease; Amyloid precursor protein beta amyloid; Luteinizing hormone; Testosterone.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Alzheimer Disease / metabolism*
Amyloid beta-Peptides / metabolism*
Animals
Humans
Luteinizing Hormone / metabolism*
Testosterone / metabolism*

Substances

Amyloid beta-Peptides
Testosterone
Luteinizing Hormone