Traumatic brain injury: cause or risk of Alzheimer’s disease? A review of experimental studies

Abstract

Traumatic Brain Injury is the leading cause of death and disability among young individuals in our society. Moreover, according to some epidemiological studies, head trauma is one of the most potent environmental risk factors for subsequent development of Alzheimer's disease. Interestingly, pathological features that are present also in Alzheimer's disease (in particular deposition of beta-amyloid protein) were observed in traumatised brains already a few hours after the initial insult. The primary objective of this review is to present methodology and results of numerous recent human and animal studies dealing with this issue. Special emphasis was placed on head trauma experiments in transgenic mouse models of Alzheimer's disease. We further evaluate the connection between traumatic brain insults and subsequent development of dementia and try to differentiate between primary and secondary pathological mechanisms.

Amyloid Precursor Protein Revisited

“…On the other hand, the transient and restricted nature of APP accumulation suggests that it is secondary to axonal damage rather than serving a primary role in the TBI response. In this regard, it is worth noting that TBI has been associated with increased risk of dementia (41). However, a consistent relationship between TBI and amyloid pathology has been difficult to establish in mouse models (41).…”

Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer's Disease

“…The two characteristic neuropathologies of Alzheimer's disease are the abnormal accumulation and deposition of amyloid-␤ peptides and tau proteins in the brain. Evidence from humans [40][41][42] and experimental animal models [43] has also revealed abnormal accumulations of amyloid-␤ peptides and tau proteins in the brain and in cerebrospinal fluid following TBI. Interestingly, elevation of plasma tau levels has been associated with increasingly severe outcomes of TBI [44].…”

Current Understanding and Experimental Approaches to the Study of Repetitive Brain Injury

“…A correlation between the occurrence of TBI and the further development of neurodegenerative disease later in life has been recognized for several years, and TBI is considered to be one of the most robust risk factors for developing Alzheimer's disease (AD; Szczygielski, et al, 2005;Slemmer et al, 2011). There is also evidence that genetic predisposition may increase one's risk of developing AD, such as possession of the apolipoprotein E 4 allele (Isoniemi et al, 2006).…”

“…Although high levels of Aβ have clearly been demonstrated in AD patients, the exact function of amyloid protein has not been established. Interestingly, deposition of Aβ has not been observed in the majority of nontransgenic animal studies after trauma (Laurer et al, 2001;Szczygielski, et al, 2005), and as a result, many of the current models used to investigate traumatic dementia are derived from transgenic rodents that were originally created to investigate AD. For example, the transgenic mouse Tg2576, which is characterized by AD-like amyloidosis by nine months of age, has been used in several investigations of repetitive mild TBI, and has become a popular animal model for traumatically-induced dementia.…”