Alzheimer?s disease: the impact of age-related changes in reproductive hormones

Abstract

The relationship between hormones and Alzheimer's disease (AD) has been intensely researched. While the majority of this work has focused on the sex steroids, estrogens, and more recently androgens, a serendipitous patient encounter led one of us (R.L.B.) to question whether other hormones of the hypothalamic-pituitary-gonadal axis might play a role in the pathogenesis of AD. The age-related decline in reproductive function results in a dramatic decrease in serum estrogen and testosterone concentrations and an equally dramatic compensatory increase in serum gonadotropin concentrations. Indeed, there is growing evidence that the gonadotropin luteinizing hormone, which regulates serum estrogen and testosterone concentrations, is an important causative factor in the development of AD. This review provides information supporting the 'gonadotropin hypothesis'. We put forth a novel mechanism of how changes in serum luteinizing hormone concentrations could contribute to the pathogenesis of AD and discusses potential therapeutic anti-gonadotropin compounds.

Towards a Unifying Hypothesis of Alzheimers Disease: Cholinergic System Linked to Plaques, Tangles and Neuroinflammation

“…This review attempts to address these questions with a focus on the central role played by cholinergic system. Therapeutic approaches based on mechanistic pathways associated with the distinct neuropathological features of AD have been extensively discussed [6][7][8][9][10][11][12][13][14], but the emerging relationship between the markers of this disease has not received its due attention. Discussion of the recent important developments [1,[15][16][17] on the convergence of the different mechanisms of AD is presented here.…”

“…has been made in different aspects of the disease [13,[30][31][32]. Advances in understanding the genetic basis of AD have shown that mutations in genes associated with the different proteins -amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) -and the presence of apolipoprotein ε4 (ApoE4) increases the risk of inheriting the disease [33].…”