Gender Differences in Frontotemporal Lobar Degeneration (FTLD) Support an Estrogenic Model of Delayed Onset

Abstract

Gender differences in frontotemporal lobar degeneration (FTLD) have been reported in the literature but not well characterized or explored. In the present work, we propose that steroid hormone estrogens delay the onset of FTLD in pre-menopausal women compared to age equivalent men, and may provide neuroprotection in the early postmenopausal period. We present a model wherein estrogens serve a regulatory role in attenuating the microglia conversion from the benign to active form in response to cell stress that might otherwise trigger an inflammatory response. Via microglia stabilization, estrogens preserve the homeostasis of both the ubiquitin-proteosome degradation system and lysosome-autophagy recycling system. Both systems have been implicated in the genetic forms of FTLD, with the latter system recognized to be associated with the majority of them.

White Matter Hyperintensities and Cortical Atrophy are associated with Neuropsychiatric Symptoms in Neurodegenerative and Cerebrovascular Diseases

“…has been reported to have more apathy and psychotic symptoms and less empathy as major predictors of disease progression [71,96,121]. A recent study found that females with bvFTD performed better on executive function task and displayed fewer NPS, particularly apathy, sleep disturbance, and appetite changes than males, despite showing similar amount of atrophy burden [122], which may support the neuroprotective role of oestrogen hormone in females [123]. Conversely, the progression of AD in which females account for majority of the diagnosis [124], has been more frequently associated with the presence of depressive symptoms [112], in line with the notion that females use more antidepressants and males more antipsychotics [106,115].…”