Cerebral amyloid angiopathy (CAA)

This is the term used to describe the accumulation of Aβ in the walls of blood vessels in the brain. Most patients with Alzheimer's disease develop CAA. Dr Katy Chalmers, Professor Gordon Wilcock and Professor Love found the severity of CAA in Alzheimer's disease to be strongly associated with inheritance of a particular variant - the ε4 variant – of a gene called APOE, that is known to confer a strong genetic risk for the development of Alzheimer's disease. The group also demonstrated that the Alzheimer's disease patients who have most severe CAA tend to have less Aβ in the form of plaques in the brain tissue; these patients seem to clear Aβ from their brain tissue only to have it deposit in the walls of their blood vessels. Some normal elderly people also develop CAA but this tends to relatively mild and the group also found that this 'normal' development of CAA with age, unlike that in Alzheimer's disease, is not associated with APOE ε4.

Further work that also involved Sharron Williams, a postgraduate student who worked under Professor Love in the Dementia Research Group lab, indicated that the accumulation of Aβ in blood vessels causes secondary changes in the immediately adjacent parts of the brain – in particular, damage to the internal ‘skeleton’ of the nerve cells, manifesting in the formation of structures known as neurofibrillary tangles and neuropil threads. In contrast, Dr Katy Chalmers, Professor Gordon Wilcock and Professor Love reported that CAA seems to play only a minor role in the development of damage in the deep nerve fibre tissue (white matter) in Alzheimer's disease; this latter damage is more closely related to the accumulation of Aβ in the brain tissue itself.

 

In a multinational study, Professor Neil Scolding (also in the Institute of Clinical Neurosciences in Bristol), several collaborators and Professor Love defined the clinical, radiological and pathological features of a rare disorder (Aβ-related angiitis, or ABRA) caused by an inflammatory reaction to Aβ in blood vessels and plaques. The changes in ABRA resemble those in patients with Alzheimer's disease who were injected with Aβ as part of a therapeutic trial and developed a meningoencephalitis, but in patients with ABRA the inflammatory reaction occurs spontaneously rather than as a result of injection of Aβ.

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