Investigating the Scientific Hypotheses Surrounding Alzheimer's Disease

by Rakhi Khurana

Advocating for brain wellness requires embracing a comprehensive holistic approach. This enables us to move away from a rigid perspective on cognitive disorders. Brain wellness is fundamental for optimal cognitive performance, overcoming emotional adversity, regulating autonomous physiological functions (heart rate, breathing and blood pressure) , enabling focus, exhibiting neuroplasticity and fostering relationships with family and friends. 

Alzheimer's disease (AD) is a neurodegenerative condition marked by substantial and gradual deterioration in cognitive function and retention. Yet, a limited comprehension of the intricate causes of AD poses challenges in preventing its initiation and slowing its progression.  Approximately 5% of  Alzheimer's disease cases are attributed to epigenetic forms (how environmental factors and life experiences influence the expression of genetic traits.), while the remaining  95% are thought to arise from mitochondrial dysfunction, behavioural choices, and idiopathic mechanisms (causes of a condition or disease that are unknown). 

The hypotheses concerning Alzheimer's disease seek to offer new and established insights into its development and progression. The following theories provide some fundamental explanations for Alzheimer's disease. 

Beta Amyloid Hypothesis  

This theory proposes that the accumulation of beta-amyloid plaque (a sticky protein that gathers in the brain) is responsible for the development of AD. Under normal conditions, beta-amyloid is generated and eliminated as part of routine brain function. Nevertheless, Alzheimer's disease is characterised by an abnormal buildup of beta-amyloid in the brain. The beta-amyloid proteins cluster together, creating non-dissolvable plaques in the gaps between nerve cells. The accumulated beta-amyloid is thought to cause harmful effects on neurons, interfering with cell-to-cell communication and initiating the activation of immune cells. This immune response leads to inflammation, ultimately resulting in the destruction of brain cells. Preventing the build up of beta amyloid protein has no definitive answer. The recommended approaches to potentially lower the risk of brain plaques include consistent physical exercise, maintaining a healthy sleep routine, participating in intellectual activities, and adopting an anti-inflammatory diet.

Tau Hypothesis  

The theory proposes that the build-up of irregular tau proteins disturbs the structure and stability of nerve cells by creating tangles in the brain. The proteins interfere with neuronal function and cause synaptic dysfunction, especially in brain regions essential for cognitive processes. Tau tangles contribute to cell death and disrupt the transport of nutrients. The precise connection between tau pathology and Alzheimer's disease remains unclear; however, continuous research aims to unravel the complex interplay between multiple factors that contribute to the development of Alzheimer's disease. 

Cholinergic Hypothesis  

This theory proposes that a deficiency in the neurotransmitter acetylcholine and other neurotransmitters, like glutamate, could result in disturbances in synaptic transmission. Acetylcholine serves as a messenger, enabling the transmission of signals between nerve cells and facilitating the smooth communication necessary for many physiological and cognitive processes. Glutamate is involved in a cycle of neurotransmitter release and recycling. Although glutamate is crucial for the typical functioning of the brain, an excessive or unregulated release of glutamate can result in excitotoxicity—a phenomenon in which the overstimulation of glutamate receptors leads to harming neurons. 

Vascular Dysfunction Hypothesis 

This hypothesis suggests that deficiencies in blood flow to the brain lead to inadequate delivery of oxygen. Vascular dysfunction might encompass alterations in the brain's smaller blood vessels, referred to as micro-vessels. Such alterations can interfere with the blood-brain barrier, potentially contributing to neuroinflammation. Systemic neuroinflammation is linked to changes in synaptic plasticity, which refers to the capacity of synapses to undergo modifications.  

 Much progress has been made in gaining a deeper understanding of the causes of  Alzheimer's disease. While many concepts remain inconclusive and are subject to further investigation, the field of biology encourages critical thinking and rigorous examination, to go beyond the fundamental notions we hold.  

This statement by Sigmund Freud, the neurologist and founder of psychoanalysis, is exceptionally fascinating. “Biology is truly a land of unlimited possibilities. We may expect it to give us the most surprising information and we cannot guess what answers it will return to the questions we have put to it” (Beyond the Pleasure Principle;1920).

References 

Beta-amyloid and the amyloid hypothesis. (n.d.). https://www.alz.org/documents/ national/topicsheet_betaamyloid.pdf  

Decourt, B., D'Souza, G. X., Shi, J., Ritter, A., Suazo, J., & Sabbagh, M. N. (2022).  The Cause of Alzheimer's Disease: The Theory of Multipathology Convergence to  Chronic Neuronal Stress. Aging and disease, 13(1), 37–60. https://doi.org/ 10.14336/AD.2021.0529 

JJ;, T. A. (n.d.). The cholinergic hypothesis of age and alzheimer’s disease-related  cognitive deficits: Recent challenges and their implications for novel drug  development. The Journal of pharmacology and experimental therapeutics. https:// pubmed.ncbi.nlm.nih.gov/12805474/ 

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Mohandas, E., Rajmohan, V., & Raghunath, B. (2009, January). Neurobiology of  alzheimer’s disease. Indian journal of psychiatry. https://www.ncbi.nlm.nih.gov/ pmc/articles/PMC2738403/ 

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%2Dassociated%20protein%20(MAP).  

PIERRE, A. F. M. (2019). Biology of Freedom: Neural Plasticity, experience,and  the unconscious. ROUTLEDGE. 

Scheffer, S., Hermkens, D. M. A., van der Weerd, L., de Vries, H. E., & Daemen,  M. J. A. P. (2021). Vascular Hypothesis of Alzheimer Disease. Arteriosclerosis,  Thrombosis, and Vascular Biology, 41(4), 1265–1283. https://doi.org/10.1161/ atvbaha.120.311911