A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injury.
Traumatic brain injury (TBI) is a risk factor for developing Alzheimer's disease (AD). Additionally, TBI induces AD-like amyloid beta (Abeta) plaque pathology within days of injury potentially resulting from massive accumulation of amyloid precursor protein (APP) in damaged axons. Here, progression of Abeta accumulation was examined using brain tissue from 23 cases with post-TBI survival of up to 3 years. Even years after injury, widespread axonal pathology was consistently observed and was accompanied by intra-axonal co-accumulations of APP with its cleavage enzymes, beta-site APP cleaving enzyme and presenilin-1 and their product, Abeta. However, in marked contrast to the plaque pathology noted in short-term cases post TBI, virtually no Abeta plaques were found in long-term survivors. A potential mechanism for Abeta plaque regression was suggested by the post-injury accumulation of an Abeta degrading enzyme, neprilysin. These findings fail to support the premise that progressive plaque pathology after TBI ultimately results in AD.
Chen
Xiao-Han
XH
Department of Neurosurgery, School of Medicine, University of Pennsylvania, 3320 Smith Walk, Philadelphia, PA 19104-6316, USA.
Johnson
Victoria E
VE
Uryu
Kunihiro
K
Trojanowski
John Q
JQ
Smith
Douglas H
DH
D000293:Adolescent; D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001369:Axons / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism* / Q000401:mortality; D005260:Female; D006801:Humans; D008264:Macrophages / Q000502:physiology; D008297:Male; D017628:Microglia / Q000502:physiology; D008875:Middle Aged; D015260:Neprilysin / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism; D017741:Survivors; D055815:Young Adult
D016229:Amyloid beta-Peptides; D016900:Neurofilament Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D015260:Neprilysin