The quest to find a cure for Alzheimer’s disease

Since the time Alois Alzheimer, a German neuropathologist noticed hitherto undescribed abnormal deposits of protein lumps in the brain (1906) sample of 50 year old Auguste D, a patient who suffered memory problems, language dysfunction, and peculiar ideas, the quest for a cure for Alzheimer’s disease has become the Holy Grail for neuroscience researchers. Patients with Alzheimer’s disease insidiously develop memory impairment, linguistic failure, personality changes, visuo-spatial dysfunction producing wandering, and apraxia resulting in the inability to perform learned tasks. The course is inexorably progressive and ultimately leaves the patient’s persona bereft of a definitive identity. Over the last 113 years of research, much has been learnt about Alzheimer’s disease albeit with the conviction that much more needs to be discovered.

This neurodegenerative disease is characterized by abnormal deposition of abnormally pleated lumps of a protein called beta-amyloid enmeshed in cellular debris within the brain interstitium, known as neuritic plaque. Concomitantly, a neuronal transport protein called Tau also gets abnormally phosphorylated and deposited within nerve cells, producing synaptic failure and cell death. This lump is called neurofibrillary tangle. The location of tangles within the brain and their density correlate with the spectrum and severity, respectively of the disease. A prior history of head injury, diabetes mellitus, sedentariness, specific inherited genes, and dysfunctional sleep parameters are now known to be risk factors for an individual susceptibility for Alzheimer’s disease. The genes Presenilin one and two and homozygosity for epsilon ApoE4 are distinct susceptibility genes that have been studied till date. The recent discovery that sleep exclusively activates a distinct excretory system within the brain known as the Glymphatic Pathway, has spawned a plethora of research correlating sleep hygiene with susceptibility to Alzheimer’s disease. The glymphatic pathway is responsible for clearing beta-amyloid and tau in healthy individuals during sleep on a daily basis.

An additional startling discovery has been the pathogenicity of an organism called PorphyromonasGingivalis. The occurrence of gingivitis due to this bug, correlates with the direct surge in the risk for precipitation of Alzheimer pathology in the patient’s brain. The bacterium produces a chemical called gingipain which precipitated phosphorylation of tau and formation of tangles in the brain. Regrettably, current therapies are not curative. Supportive medications enhance depleted neurotransmitter acetylcholine and reduce the deleterious effects of the neurotransmitter glutamate. Sleep research is paving the way for consideration of sleep modification as a preventive strategy to reduce susceptibility to Alzheimer’s disease. CPAP therapy for comorbid obstructive sleep apnea in patients with Alzheimer’s disease has improved symptom burden and quality of life. This strengthens the sleep Alzheimer relationship understanding. At present, preventive strategies to reduce the risk of susceptibility to Alzheimer’s disease includes cardiovascular exercise, mindfulness, sleep hygiene, acquisition of new skills in middle-life, and a rich and rewarding social network or connectivity.

Urgent efforts are needed in unmasking mechanisms that perpetuate the mechanisms responsible for Alzheimer’s disease.

*Disclaimer: The article has been contributed by Dr Joy Desai, Consultant of Neurology at Jaslok Hospital and Research Centre. The opinions are the personal opinions of the author. Deccan Chronicle does not hold any liability and responsibility for the same.