Abstract
With the expand of the population’s average age, the incidence of neurodegenerative disorders has dramatically increased over the last decades. Alzheimer disease (AD) which is the most prevalent neurodegenerative disease is mostly sporadic and primarily characterized by cognitive deficits and neuropathological lesions such as amyloid -β (Aβ) plaques and neurofibrillary tangles composed of hyper- and/or abnormally phosphorylated Tau protein. AD is considered a complex disease that arises from the interaction between environmental and genetic factors, modulated by epigenetic mechanisms. Besides the well-described cognitive decline, AD patients also exhibit metabolic impairments. Metabolic and cognitive perturbations are indeed frequently observed in the Developmental Origin of Health and Diseases (DOHaD) field of research which proposes that environmental perturbations during the perinatal period determine the susceptibility to pathological conditions later in life. In this review, we explored the potential influence of early environmental exposure to risk factors (maternal stress, malnutrition, xenobiotics, chemical factors … ) and the involvement of epigenetic mechanisms on the programming of late-onset AD. Animal models indicate that offspring exposed to early-life stress during gestation and/or lactation increase both AD lesions, lead to defects in synaptic plasticity and finally to cognitive impairments. This long-lasting epigenetic programming could be modulated by factors such as nutriceuticals, epigenetic modifiers or psychosocial behaviour, offering thus future therapeutic opportunity to protect from AD development.
Highlights
Alzheimer disease (AD), for which only symptomatic treatments are currently available, is a chronic neurodegenerative disorder and the most prevalence form of dementia
In AD, spreading of the neurofibrillary lesions in the cortex fits to the progression of the Perinatal Programming of Alzheimer disease symptoms, supporting that Tau pathology is instrumental in cognitive alterations
The pathophysiological mechanisms linking AD, insulin resistance and impaired glucose homeostasis remain to be clarified, it has been reported that amyloid -β (Aβ) oligomers impair insulin signalling by promoting insulin neuronal receptor internalization (Zhao et al, 2008) and inhibit insulin receptor substrate (IRS) 1 (Bomfim et al, 2012)
Summary
Alzheimer disease (AD), for which only symptomatic treatments are currently available, is a chronic neurodegenerative disorder and the most prevalence form of dementia. Numerous epidemiological studies in humans and experimental works in animals have clearly reinforced the idea that adverse perinatal environment, such as maternal stress, exposure to toxics and early-life malnutrition, has long-term consequences and may program, in the offspring, chronic adult diseases such as glucose dyshomeostasis and energy metabolism impairments and cognitive disorders (Moody et al, 2017; Gawlińska et al, 2021b), all being encountered in AD patients In light of these observations, altered perinatal neurodevelopment might sensitize to the occurrence of late-onset AD (Moceri et al, 2000; Landrigan et al, 2005; Miller and O’Callaghan, 2008; Modgil et al, 2014; Athanasopoulos et al, 2016) presumably via epigenetic mechanisms (Gapp et al, 2014; Lemche, 2018). Epigenetic mechanisms have broad actions but may mainly regulate 3 biological functions: DNA and RNA methylation, chromatin remodelling and expression of non-coding RNAs
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
