A Lack of Amyloid β Plaques Despite Persistent Accumulation of Amyloid β 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 (A beta) plaque pathology within days of injury potentially resulting from massive accumulation of amyloid precursor protein (APP) in damaged axons. Here, progression of A beta 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, A beta. However, in marked contrast to the plaque pathology noted in short-term cases post TBI, virtually no A beta plaques were found in long-term survivors. A potential mechanism for A beta plaque regression was suggested by the post-injury accumulation of an A beta degrading enzyme, neprilysin. These findings fail to support the premise that progressive plaque pathology after TBI ultimately results in AD.