The unsolved relationship of brain aging and late-onset Alzheimer disease.
Late-onset Alzheimer disease is the most common form of dementia and is strongly associated with age. Today, around 24 million people suffer from dementia and with aging of industrial populations this number will significantly increase throughout the next decades. An effective therapy that successfully decelerates or prevents the progressive neurodegeneration does not exist. Histopathologically Alzheimer disease is characterized by extensive extracellular amyloid beta (Abeta) plaques, intracellular neurofibrillary tangles (NFTs), synaptic loss and neuronal cell death in distinct brain regions. The molecular correlation of Abeta or NFTs and development of late-onset Alzheimer disease needs further clarification. This review focuses on structural and functional alterations of the brain during aging, age-associated imbalances of defences against oxidative stress and age-related alterations of the metabolism of Abeta, via a comparison of observations in healthy aged individuals and cognitively impaired or AD patients. Although our understanding of brain region-specific neuronal aging is still incomplete, the early structural and molecular changes in the transition from cognitive health to impairment are subtle and the actual factors triggering the severe brain atrophy during LOAD remain ambiguous.
Kern
Andreas
A
Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University Mainz, Duesbergweg 6, D-55099 Mainz, Germany.
Behl
Christian
C
D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D003704:Dementia / Q000378:metabolism / Q000473:pathology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology
D016229:Amyloid beta-Peptides; D005609:Free Radicals