Mitochondria‐associated endoplasmic reticulum membranes: At the crossroad between familiar and sporadic Alzheimer's disease

Abstract

Alzheimer's disease (AD), an incurable chronic neurodegenerative disease first described by Alois Alzheimer in 1906, has become a significant public health priority. After 10-15 years of preclinical stage, the symptoms develop from mild cognitive impairment to impaired memory, language difficulties and, at last, death in an average time of seven to ten years after diagnosis.After more than one hundred years of research, researchers had made tremendous progress. Nevertheless, Alzheimer's disease is still marked histologically by the accumulation of amyloid beta (Aβ), the emergence of neurofibrillary tangles, and loss of synapse. However, recently, with endless failure in clinical trials, some researchers are now turning to other symptoms such as aberrant lipid metabolism (Hamilton et al., 2015), abnormal calcium transfer (Dolev et al., 2013), and autophagic malfunction (Li et al., 2017). Mitochondria-associated endoplasmic reticulum membrane (MAM) is pivotal for the pathways mentioned above, which are disturbed in AD. Thus, Area-Gomez et al. proposed that disturbed MAM function is a "coherent and unified explanation" for both familial and sporadic AD: MAM hypothesis (Area-Gomez et al., 2012).In this review, we update the knowledge about MAM's role in pathologies shared by familial and sporadic forms of AD. We also highlight the importance of AD models used in studies.

Hypothesis and Theory: Characterizing Abnormalities of Energy Metabolism Using a Cellular Platform as a Personalized Medicine Approach for Alzheimer’s Disease

“…Because aging itself is one of the major determinants of LOAD, many pathological events in LOAD are also part of the normal aging process (Mattson and Arumugam, 2018). Thus, LOAD appears to be characterized by a combination of several interacting pathological events that are closely related to changes with age and that include, among others, altered bioenergetic, metabolic, microvascular, and inflammatory processes (Wingo et al, 2012;Herrup, 2015;Amtul, 2016;Harrison and Owen, 2016;Stoeckel et al, 2016;de la Monte, 2017;Mastroeni et al, 2017;Mattson and Arumugam, 2018;Chow et al, 2019;Long and Holtzman, 2019) as well as abnormalities of cell membranes and membranous elements, including endosomes, ER, and mitochondria (Zubenko et al, 1984(Zubenko et al, , 1987Sihag et al, 1994;Wang and Zhang, 2021). Targeting and ameliorating even one of these major causative elements might reduce the occurrence or progression of LOAD.…”

Dual Role of NMDAR Containing NR2A and NR2B Subunits in Alzheimer’s Disease

“…Alzheimer's disease (AD) is a neurodegenerative disorder that affects memory and other cognitive functions [1] and has become one of the most burdening diseases in this century [2]. The disease is classified into familial AD and sporadic AD [3]. Familial AD is induced by mutations in β-amyloid precursor protein and presenilin 1/2, and accounts only for 0.5% of AD cases, while the sporadic form is caused by hereditary together with environmental risk factors and is the dominant type of AD [4].…”