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Modifiable pathways in Alzheimer’s disease: Mendelian randomisation analysis

BMJ 2017; 359 doi: (Published 07 December 2017) Cite this as: BMJ 2017;359:j5375

Re: Modifiable pathways in Alzheimer’s disease: Mendelian randomisation analysis

RBC Acetyl choline esterase: early diagnostic biomarkers for Dementia

Alzheimer’s disease (AD) is a most devastating neurological diseases affecting about 5.2 million Americans (1), in India it is 1-3%. Studies have show that Patho-physiological changes occur decades before the appearance of the first symptoms in AD (2). 25% of all people aged 55 do have family history of dementia (2, 3, 4). AD is slow progressive neuronal degenerative diseases over period of years with mild to severe memory and cognitive loss. Beta amyloidal (AB) plaque and hyperphoshorylated TAU deposition into neurofibrilatory tangles (NFT) characterize the pathological changes most noted located in hippocampus and entorhinal region (3).

In AD there is deficiency of acetyl choline, its synthetic enzymes choline transferase (CAT) and nicotinic cholinergic receptors due to degeneration and death of cholinergic neurons, and neuronal death has been linked to dysfunction of choline uptake mechanism. ACHE has a important role in neuronal development, including regular cell growth, or cell adhesion may activate neuronal repair in AD brain and influence the neurodevelopment. Out of two types of tetrameric and monomeric ACHE molecules in AD brain there is selective loss of the tetrameric form. In a rural setting in India and developing countries advance neuroimagings, CSF study of AB42, T-tau and P-tau, hypometabolism on fluorodeoxyglucose (FDG)PET and genetic study is impossible( 5); in such situations, we evaluated RBC ACHE level as a simple cheap and easily available biomarker for early prediction of dementia in asymptomatic population the first generation relatives of AD (unpublished data). We concluded that one should be cautious in advising ACHE inhibitors in these cases.

In India relatives are tired with extensive investigation and economic loss due to repeated CT and MRI scans. Hence at the end stage, a victim of dementia including AD is totally neglected by family and just isolated in a dirty room with unclean bedding for years.

Yours truly,

Himmatrao Saluba Bawaskar MD
Pramodini Himmatrao Bawaskar MBBS
Parag Himmatrao Bawaskar MBBS

Bawaskar Hospital and research center Mahad raigad Maharashtra india 402301

1 Towards a better life with Alzheimer’s diseases. Lancet 2014;383:1100.
2 Jack CR, JR, Knopman DS, Jagust WJ et al. Hypothetical model of dynamic biomarkers of Alzheimer’s pathological cascade. Lancet neurology 2010;9:119-28.
3 Aprahamian I, Stella F and Forlenza OV. New treatment strategies for Alzheimer’s disease: is there s hope? Indian Journal of Medical Research 2013; 138:449-60.
4 Mayeux R. Early Alzheimer’s disease. New Eng.J.Med 2010;362:2194-20
5 Jack CR JR, Knopman DS, Jagust WJ etal. Tracking pathophysiology processes in Alzheimer’s disease: an updated hypothetical model of dynamic biomarkers. Lancet neurology 2013;12:207-16.

Competing interests: No competing interests

11 December 2017
Himmatrao Saluba Bawaskar
Parag himmatrao Bawaskar , Pramodini Himmatrao Bawaskar
Bawaskar Hospital &Clinical Research center Mahad Raigad Maharashtra India 402301
H.S.Bawaskar MD Mahad Raigad 402301 India