Sex Hormones and Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is the most common type of dementia and the most common neurodegenerative disorder of elderly. It is not an accelerated form of aging but it is characterized by distinct temporospatial brain pathological changes, including amyloid plaques accumulation, neurofibrillary tangles deposition, synaptic loss and neuronal death with gross brain atrophy. These changes result in persistent progressive memory and cognitive decline interfering with the usual daily activities. AD is a multifactorial disorder results from the interaction of genetic, epigenetic, environmental and lifestyle factors. Estrogen, progesterone and androgen effects are important building stones in AD pathogenesis, and their effect in brain modulation and development results in different gender susceptibility to the disease. These sex hormones whether gonadal or neurosteroids (synthesized locally in the brain) play important neuroprotective roles influencing the individual's vulnerability to AD development, rate of mild cognitive impairment (MCI)/AD conversion and speed of AD progression. Despite the little therapeutic implications of hormonal replacement therapy in AD treatment, yet this topic still represents a challenging hopeful way to construct a strategy for the development of personalized, gender-specific AD management.

Sex Differences and Role of Gonadal Hormones on Glutamate Level, After Spinal Cord Injury in Rats: A Microdialysis Study

“…As a neuroprotective agent, testosterone acts through multiple mechanisms, including attenuation of synaptic stripping (Bahnasy, El-Heneedy, & El-Seidy, 2018; Jones, Durica, & Jacob, 1997) and Glial Fibrillary Acidic Protein (GFAP), mediation of the central glial response (Coers, Tanzer, & Jones, 2002; Delchev & Georgieva, 2018; Jones, Coers, Storer, Tanzer, & Kinderman, 1999), and enhancement of the antioxidant enzymes (Ahlbom, Prins, & Ceccatelli, 2001), heat shock protein expression (Mancuso et al, 2018; Tetzlaff, Tanzer, & Jones, 2007; Zhang et al, 2004), ribosomal response (Kinderman & Jones, 1993), and the neurotrophin brain-derived neurotrophic factor (Verhovshek, Cai, Osborne, & Sengelaub, 2010).…”