| Autor: |
Maarouf CL; The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Kokjohn TA; Department of Microbiology, Midwestern University, Glendale, Arizona, United States of America., Walker DG; Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Whiteside CM; The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Kalback WM; The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Whetzel A; Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Sue LI; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Serrano G; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Jacobson SA; Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Sabbagh MN; Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Reiman EM; Banner Alzheimer's Institute, Phoenix, Arizona, United States of America., Beach TG; Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, Arizona, United States of America., Roher AE; The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, Arizona, United States of America. |
| Abstrakt: |
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. |
