Role of Testosterone on Beta-Amyloid peptide of Alzheimer's disease

[Truncated] Alzheimer's disease (AD) is a neurodegenerative disorder, characterised by the deposition of a 4kD peptide, ?-amyloid (A?), in the extracellular space of the brain, as amyloid plaques and amyloid deposits in and around blood vessels of the brain. These insoluble deposits are toxic to neurons and mainly develop in cortical areas associated with memory and learning. They are therefore thought to be the principal cause of neuronal death and the subsequent loss of cognitive functions leading to dementia observed in AD. A? is a catabolic product of a larger protein - the ?-amyloid precursor protein (APP). It is known that factors such as ageing and cytokines can affect the catabolism processing of APP, For example, oestrogen is reported to favourably promote the non-amyloidogenic processing of APP to preclude the formation of neurotoxic A?. In addition, oestrogen has also been reported to attenuate A? toxicity and promotes the clearance of AA? deposits, thereby earning its reputation as a putative candidate in the prevention of AD. However, unlike oestrogen the role of testosterone in AD has received little attention. Currently available data indicated that testosterone may also promote non-amyloidogenic processing of APP and prevent hyperphosphorylation of tau (?) protein (a pathological hallmark of AD). Furthermore, testosterone levels have also been reported to be decreased in AD. A potential mechanism is thereby postulated linking testosterone to the abnormal accumulation of A? seen in AD.