Pathophysiology of Alzheimers



Pathophysiologyof Alzheimer’s Disease


Alzheimer’sdisease (AD) is a progressive dementia condition characterized byloss of neurons and the occurrence of intracellular neurofibrillarytangles and extracellular amyloidal plaques (Ballard,Gauthier, Corbett et al. 2011).In simpler terms Alzheimer’s disease arises as a result of synapsesand loss of neurons from the cerebral cortex and the sub corticalregions. The loss leads to gross atrophy in the affected areas. On aprogressive phase Alzheimer’s disease leads to the degeneration ofparietal lobe in the temporal lobe, parts of the frontal cortex andin the cingulated gyrus region. Degeneration is also prevalent in thelocus coeruleus (Heneka,2015).The presence of amyloidal plaques is dense, insoluble depositsmaterials that form around neurons. Neurofibrillary tangles aremicrotubules that accumulate inside the cells (Ballard,Gauthier, Corbett A et al. 2011).Many old people develop some plaques and tangibles due to ageing butindividuals with AD have higher numbers in the brain regions such asin the temporal lobe.

Thebiochemistry of Alzheimer`s disease

Alzheimer`sdisease is characterized by protein misfolding condition(proteopathy) that is caused by the accumulation of plaque (misfoldedtau and amyloidal beta proteins) in the brain. Plaques comprises ofsmall peptides that in turn carries amino acids (amyloidal beta).Amyloidal beta fragments from Amyloidal precursor protein (APP) andthis protein penetrates the neuron membrane (Heneka,2015).APP is essential for the growth, survival and repair of neurons. Inthe event of AD, an undistinguished enzyme that arises fromproteolytic process leads to the fragmentation of APP into smallerparts. It is these smaller parts of APP that are amyloidal beta thatform clumps and deposits around the neurons (Ballard,Gauthier, Corbett A et al. 2011).

Thefragmented APP form dense senile plaques around neurons which in turnlead to their degeneration. Each neuron has support structures thatare known as microtubules that act like tracts in guiding nutrientsfrom the body of cells to the end of axion and back. Tau proteinhelps in stabilizing the microtubules during phosphorylation (Heneka,2015).In AD an abnormal aggregation of tau protein occurs due to chemicalchanges and begins to pair with other threads resulting in thedisintegration of the neuron’s transport system(Ballard, Gauthier, Corbett A et al. 2011).


Ithas not been established how the aggregation and production ofbeta-amyloidal peptides leads to the pathological AD condition(Heneka, 2015).Traditional hypothesis points that the accumulation of beta-amyloidalpeptides as the main influences leading to neuron degeneration.Amyloidal fibrils are believed to be toxic and disrupt the formationof proteins that help in altering abnormal chemical process in neuroncells (Ballard,Gauthier, Corbett et al. 2011).Beta-amyloids build up in mitochondria cells of Alzheimer’saffected brain regions. Beta-Amyloidal also leads to the inhibitionof certain enzyme functions as well as the utilization of glucose byneuron cells. The pathology of AD is also attributed to variousinflammatory processes and cytokine(Querfurth and LaFerla, 2010).

Inflammationis tissues damage that is either primary or secondary and in AD casesinflammation signifies immunology response (Ballard,Gauthier, Corbett et al. 2011).Emerging studies indicates that the interaction of neurons andimmunological mechanisms in the brain leads to the AD condition(Querfurthand LaFerla, 2010).Other studies indicate that systemic inflammation and obesity leadsto the progression of AD. Further studies, indicate that thealteration in the distribution of neuropathic elements and receptorsexpressions lime in the case of brain-derived neurotrophic factor(BDNF) are associated with AD. Alzheimer`s disease is assessed basedon individuals’ medical history, genetic or family history andthrough behavioral observations (Ballard,Gauthier, Corbett et al. 2011).There is no definitive treatment or prevention method of AD butsuggestions have been made on diet, avoiding cardiovascular risks,pharmaceutical products and engaging in intellectual activities.

Conceptualmap of Alzheimer Disease


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BurnsA, Iliffe S (5 February 2009). &quotAlzheimer`s disease.&quot BMJ(Clinical research ed.)338:


HenekaMT (April 2015). &quotNeuroinflammation in Alzheimer`s disease.&quotLancetNeurology14


QuerfurthHW, LaFerla FM (28 January 2010). &quotAlzheimer`s disease.&quotTheNew England Journal of Medicine362(4): 329–44.