Scientists have revealed that protein clumps associated with Alzheimer’s disease are also found in the brains of people who have had a head injury.
Although previous research has shown that these clumps, called amyloid plaques, are present shortly after a brain injury – this study shows the plaques are still present over a decade after the injury.
The findings, by researchers from Imperial College London, may help explain why people who have suffered a serious brain injury appear to be at increased risk of dementia. Although extensive research now suggests major head injury increases dementia risk in later life, scientists do not know the biological changes that cause this effect.
“The consequences of a head injury have been called a hidden disability – although patients may seem to have outwardly made a good recovery, when we see them in clinic years later they can have persistent problems which affect their daily life, for example impairments in concentration and memory,” said Dr Gregory Scott, the lead author of the paper, from the Department of Medicine at Imperial.
“Research is increasingly showing that a blow to the head, such as that sustained in a road accident, triggers biological processes in the brain that burn away in the background for years,” added Dr Scott.
“Although previous research has shown that some head injury patients have these amyloid plaques shortly after the incident, these findings suggest these plaques are still present in the brains of patients over 10 years later. This helps shed light on why brain injury patients seem to be at increased risk of dementia – and may help us develop treatments that reduce this risk.”
In the research, published in the journal Neurology, the team studied nine patients with moderate to severe traumatic brain injuries. Many had sustained these in road traffic accidents, such as being hit by a car, between 11 months to 17 years prior to the study. Although they had no physical disabilities from the injury, many still suffered daily problems with memory and concentration.
The patients, who were aged between 38-55, underwent a brain scan that used a technique that allows scientists to view amyloid plaques. These proteins are thought to be a hallmark of Alzheimer’s disease, and their formation may trigger other changes that lead to the death of brain cells.
The team also scanned the brains of healthy volunteers, and people with Alzheimer’s disease. The patients with head injury were found to have more amyloid plaques than the healthy volunteers, but fewer than those with Alzheimer’s disease.
In the head injury patients, the amyloid plaques were found to be centred mainly in two brain areas: the posterior cingulate cortex – a highly active area in the centre of the brain involved in controlling attention and memory, and the cerebellum – a region at the base of the brain involved in motor control and coordination.
In a second part of the study, the team assessed damage to so-called white matter. This is the ‘wiring’ of the brain, and enables brain cells to communicate with each other. The results showed that amyloid plaque levels in the posterior cingulate cortex were related to the amount of white matter damage, suggesting that injury to the brain’s wiring may be linked to the formation of amyloid plaques.
Although this is small-scale study, explained Dr Scott, it provides hope for developing treatments in the future that may help treat the long-term effects of head injuries.
“This is a preliminary study, and it’s important to stress that these head injury patients didn’t have Alzheimer’s disease. However it supports the idea that the window of treatment for brain injury is potentially months or even years after the initial event. If we can find out exactly what processes are going on in the brain, it may be that we can intervene and improve long-term outcomes for patients.
“The works also highlights how damaging brain injury can be – and fuels the public health debate about what we can do to protect ourselves against head injuries.”
About this Alzheimer’s disease research
Source: Kate Wighton – Imperial College London Image Credit: The image is in the public domain Original Research:Abstract for “Amyloid pathology and axonal injury after brain trauma” by Gregory Scott, Anil F. Ramlackhansingh, Paul Edison, Peter Hellyer, James Cole, Mattia Veronese, Rob Leech, Richard J. Greenwood, Federico E. Turkheimer, Steve M. Gentleman, Rolf A. Heckemann, Paul M. Matthews, David J. Brooks, and David J. Sharp in Neurology. Published online February 3 2016 doi:10.1212/WNL.0000000000002413
Amyloid pathology and axonal injury after brain trauma
Objective: To image β-amyloid (Aβ) plaque burden in long-term survivors of traumatic brain injury (TBI), test whether traumatic axonal injury and Aβ are correlated, and compare the spatial distribution of Aβ to Alzheimer disease (AD).
Methods: Patients 11 months to 17 years after moderate–severe TBI underwent 11C-Pittsburgh compound B (11C-PiB)-PET, structural and diffusion MRI, and neuropsychological examination. Healthy aged controls and patients with AD underwent PET and structural MRI. Binding potential (BPND) images of 11C-PiB, which index Aβ plaque density, were computed using an automatic reference region extraction procedure. Voxelwise and regional differences in BPND were assessed. In TBI, a measure of white matter integrity, fractional anisotropy, was estimated and correlated with 11C-PiB BPND.
Results: Twenty-eight participants (9 with TBI, 9 controls, 10 with AD) were assessed. Increased 11C-PiB BPND was found in TBI vs controls in the posterior cingulate cortex and cerebellum. Binding in the posterior cingulate cortex increased with decreasing fractional anisotropy of associated white matter tracts and increased with time since injury. Compared to AD, binding after TBI was lower in neocortical regions but increased in the cerebellum.
Conclusions: Increased Aβ burden was observed in TBI. The distribution overlaps with, but is distinct from, that of AD. This suggests a mechanistic link between TBI and the development of neuropathologic features of dementia, which may relate to axonal damage produced by the injury.
“Amyloid pathology and axonal injury after brain trauma” by Gregory Scott, Anil F. Ramlackhansingh, Paul Edison, Peter Hellyer, James Cole, Mattia Veronese, Rob Leech, Richard J. Greenwood, Federico E. Turkheimer, Steve M. Gentleman, Rolf A. Heckemann, Paul M. Matthews, David J. Brooks, and David J. Sharp in Neurology. Published online February 3 2016 doi:10.1212/WNL.0000000000002413