Joseph Jebelli John Murray, 2017, HB, 320pp, £18.99, 978-1473635739
Joseph Jebelli is a researcher at the Institute of Neurology at University College London, working on rats genetically programmed to develop Alzheimer’s disease — specifically, on immune stimulation of microglial cells in the hope that this will make some contribution to an eventual cure.
He begins with an account of the first formal description of the disease by Alois Alzheimer in 1906, whose presentation to a psychiatric convention was met with a distinctly uninterested response from his psychoanalytically inclined audience. His work was rewarded in 1910 when Kraepelin, in his Handbook of Psychiatry, used the term ‘Alzheimer’s disease’ for the first time.
Moving on to describe the major research findings to date, we read about the discovery of plaques and tangles, the two microanatomical hallmarks of Alzheimer’s, and the later discovery that acetylcholine activity was diminished in the brains of sufferers. Further work elucidated the significance of beta-amyloid, bolstered by the finding of a single nucleotide mutation on chromosome 21 in familial early-onset Alzheimer’s, which causes the production of amyloid precursor protein (APP). The three overlapping but competing theories of causation include the beta-amyloid cascade theory, which contends that the deposition of amyloid is the primary precipitant; the apoprotein 4 theory, which focuses on the role of impaired glucose uptake in diseased brains; and the tau theory, tau (tubule-associated unit) being a protein found in tangles that disrupts intra-neuronal transport and causes neuronal degeneration and death.
The section on prevention focuses on the usual suspects: stress, diet, exercise, brain training, and sleep. A gallop through the evidence leads to the predictable conclusion that, though none of these options offers any dramatic promise, in the author’s words:
’… these lifestyle measures are good for us anyway, [so] play it safe … follow a Mediterranean diet. Exercise. Avoid stress. Stimulate your mind. Sleep. You’ve got nothing to lose and everything to gain.’
The remaining chapters take us all over the globe, through a number of cutting-edge research projects in neurobiochemistry, and some tantalising possibilities. Plasma infusions can improve memory, perhaps through proteins that stimulate neurogenesis in the hippocampus. Prions, virus-like proteins that include the entities responsible for CJD and kuru, seem also to have some protective function. The observation that cancer susceptibility and Alzheimer’s are negatively correlated has led to speculation about the possibility of using certain chemotherapeutic agents early in the disease. And the fact that the low prevalence of Alzheimer’s in Iceland is due to a single protective mutation at the same site as the mutation that causes early-onset Alzheimer’s offers some hope for drug treatment aimed at amyloid production and breakdown. A village in India provides a case study for the possible protective effects of turmeric, while a village in Colombia by contrast has a concentration of another familial form of the disease characterised by a distinctive form of ‘cotton wool’ plaques.
Jebelli exudes a sense of optimism, and believes that there will be an effective treatment for the disease within his lifetime. A lot of hope is pinned on gene modification, and in particular on the gene-editing tool known as CRISPR.
The author never loses sight of the human stories: those of the scientists dedicating their lives to defeating this horrible disease, but, more importantly, those of its sufferers and their families. His humanity complements his hopefulness, and his readers should be grateful for both.
- © British Journal of General Practice 2017
