Mitochondria and Alzheimer’s Disease: An Electron Microscopy Study

Abstract

Alzheimer's disease is a progressive, irreversible presenile or senile neurodegenerative disorder, implicating mainly the mental faculties, characterized by decline of memory and judgment, learning impairment, loss of professional skills and verbal capacities, alterations of social behavior, decline of motor skills and eventual disarrangement of the autonomic equilibrium. Among the pathogenetic factors, oxidative stress and mitochondrial dysfunction may play an essential role. Alterations of mitochondria may enhance amyloid toxicity, which in turn may aggravate mitochondrial dysfunction. We describe ultrastructural alterations of mitochondria in the soma of neurons, in axons, dendritic profiles and synaptic terminals, in astrocytes in early cases of Alzheimer's disease on various areas of the cerebral and the cerebellar cortex, the hippocampus, the hypothalamus, the mammillary bodies and the medial geniculate body. The morphological and morphometric study of the mitochondria revealed an impressive polymorphism at any area of the brain. The mitochondria demonstrated variation of size and shape, fragmentation of the cristae and marked changes of their structure. The most dramatic mitochondrial alterations were observed in dendritic profiles, spines and synaptic terminals. A substantial number of astrocytes demonstrated mitochondrial alterations, which coexisted with fragmentation of Golgi apparatus and dilatation of the cisternae of the smooth endoplasmic reticulum. On the basis of our observations, we feel that therapeutic strategies aiming at protecting the mitochondria might be beneficial in the treatment of early cases of AD.

Mitophagy and the Brain

“…Mitochondria in AD autopsy brain samples have fragmented cristae and vary widely in size compared to age matched ND brain samples [148]. Mitochondria within dendritic spines and presynaptic terminals show the most fragmented and disorganized cristae.…”

“…Alterations to mitochondrial ultrastructure were observed in areas of the brain with and without Aβ and tau pathology (cerebellar cortex, hypothalamus, cerebellum, and visual cortex). In addition to altered mitochondrial morphology, presynaptic terminals had reduced synaptic vesicles and fragmentation of golgi cisternae was observed [148].…”

Mitophagy and the Brain

“…Mitochondria in AD autopsy brain samples have fragmented cristae and vary widely in size compared to age-matched non-demented brain samples [ 152 ]. Mitochondria within dendritic spines and presynaptic terminals show the most fragmented and disorganized cristae.…”

“…Alterations to mitochondrial ultrastructure were observed in areas of the brain with and without Aβ and tau pathology (cerebellar cortex, hypothalamus, cerebellum, and visual cortex). In addition to altered mitochondrial morphology, presynaptic terminals had reduced synaptic vesicles and fragmentation of golgi cisternae was observed [ 152 ].…”

Editorial: Metabolism in Alzheimer's Disease

“…These findings have led to overwhelming evidence of metabolic deficiencies in AD. Beyond reductions in brain glucose metabolism, mitochondrial dysfunction is observed not only within the brain but also systemically (Parker, 1991 ; Kish et al, 1992 ; Cardoso et al, 2004a , b ; Morris et al, 2014b ; Fisar et al, 2016 ; Guo et al, 2017 ; Swerdlow, 2018 ; Baloyannis, 2019 ; Chakravorty et al, 2019 ). More recent genome wide association studies (GWAS) identified risk-associated single nucleotide polymorphisms (SNPs) in genes which function in mitochondrial and metabolic pathways (Lakatos et al, 2010 ; Swerdlow et al, 2020 ; Harwood et al, 2021 ; Wightman et al, 2021 ).…”