PowerPoint Presentation On Pathophysiology Of Alzheimer's Di

Powerpoint Presentation Onpathophysiology Of Alzheimers Diseasetani

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia worldwide. As of 2015, approximately 29.8 million people globally suffer from AD, primarily affecting individuals aged 65 and older. The disease manifests through a gradual decline in cognitive, social, and behavioral functions, ultimately impairing a person's ability to function independently. Despite extensive research, the exact etiology of AD remains unknown, although several genetic and epigenetic factors are associated with its pathophysiology.

The pathophysiology of AD involves complex molecular and cellular mechanisms. Early-onset familial AD is linked to mutations in three genes located on chromosome 21: amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). These genetic alterations lead to abnormal processing of APP, resulting in increased production of beta-amyloid (Aβ) peptides. These peptides aggregate extracellularly, forming neuritic plaques that disrupt neuronal communication and trigger neuroinflammation. In late-onset AD, a significant genetic risk factor is the presence of the apolipoprotein E epsilon 4 (APOE4) allele, situated on chromosome 19, which influences amyloid clearance and deposition.

Furthermore, epigenetic modifications such as DNA methylation influence gene expression relevant to AD. The pathological hallmarks include accumulation of extracellular amyloid plaques composed of Aβ protein and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. These tangles cause neuronal dysfunction and apoptosis, particularly in the hippocampus and cortex regions vital for memory and cognition. The tau protein detaches from microtubules in neurons, aggregates to form neurofibrillary tangles, and impairs intracellular transport, leading to neuronal death.

The neurodegeneration in AD results from the death of cholinergic neurons in the basal forebrain, leading to decreased levels of acetylcholine, a neurotransmitter crucial for learning and memory. The loss of cholinergic function correlates with the severity of cognitive deficits observed in patients. The disease progression involves widespread brain atrophy, characterized by shrinking of the hippocampus and cortex, and widening of sulci.

Body Systems Affected by Alzheimer’s Disease

While AD primarily affects the central nervous system (CNS), its impact extends to multiple body systems due to the widespread neuronal degeneration. The CNS is directly affected, with amyloid plaques and neurofibrillary tangles leading to neuronal death, which impairs cognition, behavior, and motor functions. The degeneration of cholinergic pathways also impacts other brain regions involved in processing emotions and coordination.

Alzheimer’s disease also affects the digestive system, often causing swallowing difficulties and choking risks in advanced stages. These problems stem from the impairment of brain regions responsible for motor control and swallowing reflexes. Additionally, systemic effects include weight loss and nutritional deficiencies due to reduced food intake and difficulties swallowing.

Diagnosis of Alzheimer’s Disease

The diagnosis of AD involves a comprehensive clinical evaluation by a neurologist or geriatrician. The clinical history and symptom progression are carefully reviewed. Diagnostic tests include neuroimaging modalities such as magnetic resonance imaging (MRI) and computed tomography (CT) scans to assess brain atrophy. Positron emission tomography (PET) scans help detect amyloid and tau protein deposition, especially the future use of tau-specific PET imaging.

Laboratory tests are employed to rule out other causes of cognitive impairment. Neuropsychological assessments, memory tests, and mental status examinations evaluate cognitive functions. Biomarkers like cerebrospinal fluid (CSF) analysis for beta-amyloid and tau proteins are increasingly used to support diagnosis. Emerging tools involve the detection of tau proteins via PET imaging, providing more precise evidence of AD pathology.

Treatment of Alzheimer’s Disease

Currently, there is no cure for AD. Treatment strategies aim to manage symptoms and improve quality of life. Pharmacological interventions predominantly involve cholinesterase inhibitors such as donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne). These drugs work by inhibiting the breakdown of acetylcholine, thereby enhancing cholinergic transmission and temporarily alleviating cognitive symptoms.

Additionally, N-methyl-D-aspartate (NMDA) receptor antagonists like memantine are prescribed to moderate to severe stages of AD to regulate glutamatergic neurotransmission and prevent excitotoxicity. Non-pharmacological approaches include cognitive therapies, supportive care, lifestyle modifications, and participation in support groups. Ongoing research explores disease-modifying approaches targeting amyloid and tau pathologies, although none have yet received regulatory approval.

Conclusion

Alzheimer's disease represents a significant public health challenge due to its progressive nature and devastating impact on individuals and their families. Understanding its underlying pathophysiology is crucial for developing targeted therapies and early diagnostic tools. Although current treatments do not halt disease progression, they offer symptomatic relief and improve patient quality of life. Continued research into genetic, epigenetic, and molecular mechanisms remains vital for discovering effective interventions and, ultimately, a cure.

References

• Huether, S., McCance, K., Brashers, V., & Rote, N. (2016). Understanding pathophysiology (6th ed.). Elsevier.
• Mayo Clinic Staff. (2019). How Alzheimer's is diagnosed. Mayo Clinic. https://www.mayoclinic.org
• Etindele Sosso, F., Nakamura, O., & Nakamura, M. (2017). Epidemiology of Alzheimer’s Disease: Comparison between Africa and South America. Journal of Neurology and Neuroscience, 8(4). https://doi.org/10.21767
• Alagiakrishnan, K., Bhanji, R., & Kurian, M. (2013). Evaluation and management of oropharyngeal dysphagia in different types of dementia: A systematic review. Archives of Gerontology and Geriatrics, 56(1), 1-9. https://doi.org/10.1016/j.archger.2012.04.011
• Reitz, C., & Mayeux, R. (2014). Genetic variations associated with Alzheimer disease: Implications for risk assessment, diagnosis, and therapeutics. Nature Reviews Neurology, 10(4), 206-217.
• Selkoe, D. J., & Hardy, J. (2016). The amyloid hypothesis of Alzheimer's disease at 25 years. EMBO Molecular Medicine, 8(6), 595-608.
• De Strooper, B., & Karran, E. (2016). The cellular phase of Alzheimer’s disease. Cell, 164(4), 603-615.
• Jack, C. R., et al. (2013). Tracking pathophysiological processes in Alzheimer's disease: An updated hypothetical model of dynamic biomarkers. The Lancet Neurology, 12(2), 207-216.
• Baker, S. L., et al. (2018). Biomarkers of Alzheimer’s disease: Progress and prospects. Translational Research, 200, 14-27.
• Hampel, H., et al. (2018). Blood-based biomarkers for Alzheimer’s disease: Towards targeted personalized medicine. Journal of Alzheimer's Disease, 63(2), 567-577.