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Mielke MM, Savica R, Wiste HJ, Weigand SD, Vemuri P, Knopman DS, Lowe VJ, Roberts RO, Machulda MM, Geda YE, Petersen RC, Jack CR Jr. Head trauma and in vivo measures of amyloid and neurodegeneration in a population-based study. Neurology. 2014 Jan 7;82(1):70-6. Epub 2013 Dec 26 PubMed.
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Icahn School of Medicine at Mount Sinai
I think that there a lot of uncontrolled and unknowable variables at work here. The post traumatic brain injury (TBI) amyloidosis probably peaks very early and then might be resolved completely. I assume that the propensities for depositing and the speed of clearing are both genetically determined. This means that the timing of the imaging is important. In many patients, amyloid may come and go quickly. Another major issue is that the post-TBI amyloidosis is largely diffuse amyloid, and we know that diffuse deposits are poorly detected by current ligands.
Institute of Clinical Neurobiology
Mielke et al. found that among older people with MCI but not cognitively normal (CN) individuals, those with a previous history of traumatic brain injury (TBI) have more Aß deposits in the brain than those without TBI history, suggesting that the etiology of cognitive impairment in MCI is likely more related to AD pathology than in those without TBI. These data raise questions about the relevance of TBI and PET abnormality findings in those with MCI.
Here, two problems arise:
(1) Recent evidence comparing Aß PET studies with postmortem or biopsy results raised doubts about this method as being a true representation of Aß loads in the living brain, which may have various reasons (Jack et al., 2013; Ikonomovic et al., 2012; Kepe et al., 2013). On the other hand, 55 percent prevalence of PiB positivity was observed in non-demented subjects younger than 80 years and 85 percent positivity in the ApoE4-positive non-demented elderly (Mathis et al., 2013).
(2) Epidemiology studies show that around 30 percent of patients who die from TBI have Aß plaques that are similar to those present in AD (Shively et al., 2012), suggesting that TBI is an important epigenetic risk factor of AD (Sivanandam and Thakur, 2012).
These data were in accordance with a retrospective clinico-pathologic study: Among 68 consecutive autopsy cases with a history of TBI, a total of 21.2 percent showed AD, while in a cohort of 69 age-matched cases with autopsy-confirmed AD, TBI residuals (old contusions) in frontobasal, temporal, and parietal areas were seen in 3.0 percent. These data supported the suggestion that severe TBI with long-lasting morphologic residuals is a risk factor for the development of dementia/AD (Jellinger, 2004).
While a history of a single TBI is associated with later syndromes of cognitive impairment, AD pathology after a single TBI is poorly understood. A 38-year-old man who died 16 years after a single episode of severe TBI followed by disorders of memory, behavior, and myoclonic jerks, revealed at postmortem the classical findings of AD, representing a post-traumatic premature AD (Rudelli et al.,1982). Similar chronic pathologies are commonly found years after a single moderate to severe TBI (Smith et al., 2013). Postmortem brains from long-term survivors of just a single TBI (one-47 years survival) showed neurofibrillary tangles (NFTs) in one-third and Aß plaques in two-thirds of samples, suggesting that a single TBI induces long-term neuropathologic changes akin to those found in AD (Johnson et al., 2012).
Aß plaques can be found within days of severe TBI in humans (Graham et al., 1995; Roberts et al., 1991). AD pathology, in particular diffuse cortical Aß deposits in human temporal cortex surgically excised after severe TBI, have been found as early as two hours after injury and were present in one-third of such subjects age 18-65 years (Ikonomovic et al., 2004). These and other data lend further support to the suggestion that TBI significantly increases the risk of developing pathologic and clinical symptoms of AD. Why Mielke et al. found PiB PET positivity only in MCI and not in CN subjects with a history of TBI needs further elucidation.
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