title: Biochemical assessment of precuneus and posterior cingulate gyrus in the context of brain aging and Alzheimer's disease.
abstract: Defining the biochemical alterations that occur in the brain during "normal" aging is an important part of understanding the pathophysiology of neurodegenerative diseases and of distinguishing pathological conditions from aging-associated changes. Three groups were selected based on age and on having no evidence of neurological or significant neurodegenerative disease: 1) young adult individuals, average age 26 years (n = 9); 2) middle-aged subjects, average age 59 years (n = 5); 3) oldest-old individuals, average age 93 years (n = 6). Using ELISA and Western blotting methods, we quantified and compared the levels of several key molecules associated with neurodegenerative disease in the precuneus and posterior cingulate gyrus, two brain regions known to exhibit early imaging alterations during the course of Alzheimer's disease. Our experiments revealed that the bioindicators of emerging brain pathology remained steady or decreased with advancing age. One exception was S100B, which significantly increased with age. Along the process of aging, neurofibrillary tangle deposition increased, even in the absence of amyloid deposition, suggesting the presence of amyloid plaques is not obligatory for their development and that limited tangle density is a part of normal aging. Our study complements a previous assessment of neuropathology in oldest-old subjects, and within the limitations of the small number of individuals involved in the present investigation, it adds valuable information to the molecular and structural heterogeneity observed along the course of aging and dementia. This work underscores the need to examine through direct observation how the processes of amyloid deposition unfold or change prior to the earliest phases of dementia emergence.
authors.affiliation: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Chera L
authors.initials: CL
authors.lastname: Maarouf
authors.affiliation: Department of Microbiology, Midwestern University, Glendale, Arizona, United States of America.
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
authors.affiliation: Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
authors.affiliation: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Charisse M
authors.initials: CM
authors.lastname: Whiteside
authors.affiliation: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Kalback
authors.affiliation: Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Alexis
authors.initials: A
authors.lastname: Whetzel
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Lucia I
authors.initials: LI
authors.lastname: Sue
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Geidy
authors.initials: G
authors.lastname: Serrano
authors.affiliation: Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Sandra A
authors.initials: SA
authors.lastname: Jacobson
authors.affiliation: Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
authors.affiliation: Banner Alzheimer's Institute, Phoenix, Arizona, United States of America.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.affiliation: Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
authors.affiliation: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America.
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D005260:Female; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000378:metabolism* / Q000473:pathology; D010296:Parietal Lobe / Q000378:metabolism* / Q000473:pathology; D064568:S100 Calcium Binding Protein beta Subunit / Q000378:metabolism; D055815:Young Adult; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D019208:Brain-Derived Neurotrophic Factor; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; D051844:alpha-Synuclein; D016875:tau Proteins; C579455:BDNF protein, human; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human