The most frequent form of dementia (accounting for 50-70% of all cases) is Alzheimer’s, named after Dr. Alois Alzheimer who observed changes in the brain tissue of a patient who died of the then-unknown mental illness. Here he discovered abnormalities in neurons - today called amyloid plaques and neurofibrillary tangles - with ‘plaques’ being dense, insoluble, protein deposits (small peptides, 39-43 amino acids long known as amyloid-beta AKA A-beta) and cellular material outside the neurons, which grow into ‘tangles’- twisted fibres within the nerve cell. These then result in an interruption in brain signals and eventually cell death, culminating degeneration in the temporal lobe, parietal lobe and parts of the frontal cortex and cingulate gyrus. Due to the role of amyloid-beta protein deposists, Alzheimer’s is identified as a ‘protein misfolding disease’ (Wenk, 2003; Tiraboschi et al., 2004). Amyloid beta comes from a larger ‘transmembrain’ protein (a protein that can move the neuronal membrane) known as amyloid precursor protein (or APP). APP is crucial for neuron growth and repair in healthy brains, but in Alheimer’s an as-yet unidentified process causes this to be broken down in small fragments (including fibrils of the harmful Amyloid-beta) by enzymes through a process known as ‘proteolysis’. There are also sub-types within Alzheimer’s, for example Terry Pratchett suffers from a rare early-onset form of ‘posterior cortical astrophy’, which as the name suggests is characterised by its focus on the posterior regions of the brain where visual processing occurs.

Frontotemporal dementia, also referred to as ‘frontal lobe dementia’ and ‘fontotemporal lobar dementia’, is actually an umbrella term for a particular group of pathologies that affect the frontal lobes with the best known being ‘Pick’s disease’. Frontotemporal dementia is characterised by atrophy of the frontal and anterior temporal regions (often this damage is symmetrical) and, in Pick’s disease, by ‘Pick’ bodies made up of protein inclusions in neurons. The outward symptoms of frontotemporal dementia are also slightly different and it is common for sufferers to initially experience personality change and dysphasia (an inability to comprehend or reproduce language) as opposed to forgetfulness which usually occurs at later stages. In the case of Pick’s disease these ‘protein inclusions’ are caused by an abnormal amount of tau protein which ‘clogs up’ the microtubules within the neurons of the hippocampus and numerous other areas of the brain including the dentate gyrus and the neocortex. Its distribution throughout various layers of the brain within the frontotemporal region is a distinguishing feature of Pick’s Disease. FTD also exhibits only two of the six isoforms of tau protein unlike other dementias. Unlike Alzheimer’s FTD regularly has a family history (though not in the case of Pick’s disease) and is possibly sometimes the result of a mutation on the tau protein gene located on chromosome. Other forms of frontotemporal dementia are progressive non-fluent aphasia and semantic dementia.

Another similar form of dementia is ‘dementia with lewy bodies’. Here the ‘lewy bodies’ in question are small inclusions within brain cells again formed of insoluble proteins that are nevertheless markedly different from the plaques and tangles seen in Alzheimer’s patients. Lewy bodies are instead clusters of alpha-synuclein and ubiquitin protein in brain cells. This form of dementia can be diagnosed by the fluctuating nature of its symptoms and by vivid hallucinations. The presence of Lewy bodies is normally ascertained in post-mortem biopsies.

In Vascular dementia (the second most common form), also known as multi-infarct dementia, small strokes and/or other disruptions in the brain’s blood supply result in cell death. Vascular dementia therefore is notable by its sudden on-set and patients are more likely to show signs of improvement or remain stable for long periods of time, though the strokes themselves may be ‘silent’ meaning that it can occur unnoticed. These strokes are often caused by high blood pressure. Here the seriousness of the condition depends on the region(s) of the brain in which the strokes took place.

Mack LeMouse

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