Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease that affects almost 35 million people worldwide. AD is mainly diagnosed in people over 65 years of age but the less prevalent early onset familial Alzheimer’s can occur much earlier. The familial AD is mainly caused by mutations in various chromosomal regions whereas the much more prevalent late onset sporadic AD which accounts for almost 95% of all AD cases is caused by the combined effect of various biomolecular reactions in the body that results in cognitive decline, severe memory loss, neuronal damage and ultimately death. Although the sporadic and familial AD differ in their cause and ages of onset, their pathophysiological end products are very similar (Bonda
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The disease was initially observed in a 51-year-old woman named Auguste D. Her family brought her to Dr. Alzheimer in 1901 after noticing changes in her personality and behavior. The family reported problems with memory, difficulty speaking, and impaired comprehension. Dr. Alzheimer later described Auguste as having an aggressive form of dementia, manifesting in memory, language and behavioural deficits. Dr. Alzheimer noted many abnormal symptoms, including difficulty with speech, agitation, and confusion. He followed her care for five years, until her death in 1906. Following her death, Dr. Alzheimer performed an autopsy, during which he found dramatic shrinkage of the cerebral cortex, fatty deposits in blood vessels, and atrophied brain cells. He discovered neurofibrillary tangles and senile plaques, which are indicative of AD. The condition was first discussed in the medical literature in 1907 and named after Alzheimer in 1910 (Graeber et al., 1997; Graeber et al., 1998; Graeber and Mehraein, 1999; Maurer et al., …show more content…
A-beta (Aβ) peptide is derived from amyloid precursor protein (APP) which is a transmembrane protein with a 590-680 amino acid long extracellular amino terminal domain and an approximately 55 amino acid long cytoplasmic tail which contains intracellular trafficking signals. mRNA from the APP gene on chromosome 21 undergoes alternative splicing to yield eight possible isoforms, three of which (the 695, 751 and 770 amino acid isoforms) predominate in the brain. APP695 is the shortest of the three isoforms and is mainly produced in neurons. APP751 and APP770 are mostly found in non-neuronal glial cells. All these isoforms share the same Aβ, transmembrane and intracellular domains and are thus potentially amyloidogenic. Differential proteolysis of APP by enzymes known as secretases generates Aβ variants ranging in size from 39 to 43 amino acids, of which the 40-residue Aβ40 and 42-residue Aβ42 peptides are the most common (Hartmann et al., 1997; Zhang et al., 2011). Compared to Aβ40, Aβ42 is more prone to aggregation and more neurotoxic (Dahlgren et al., 2002). It is also seen that the ratio of Aβ42/Aβ40 is elevated in most of the familial AD cases. The normal function of APP is currently unknown but it has been demonstrated to be localized in synapses where
The disease was initially observed in a 51-year-old woman named Auguste D. Her family brought her to Dr. Alzheimer in 1901 after noticing changes in her personality and behavior. The family reported problems with memory, difficulty speaking, and impaired comprehension. Dr. Alzheimer later described Auguste as having an aggressive form of dementia, manifesting in memory, language and behavioural deficits. Dr. Alzheimer noted many abnormal symptoms, including difficulty with speech, agitation, and confusion. He followed her care for five years, until her death in 1906. Following her death, Dr. Alzheimer performed an autopsy, during which he found dramatic shrinkage of the cerebral cortex, fatty deposits in blood vessels, and atrophied brain cells. He discovered neurofibrillary tangles and senile plaques, which are indicative of AD. The condition was first discussed in the medical literature in 1907 and named after Alzheimer in 1910 (Graeber et al., 1997; Graeber et al., 1998; Graeber and Mehraein, 1999; Maurer et al., …show more content…
A-beta (Aβ) peptide is derived from amyloid precursor protein (APP) which is a transmembrane protein with a 590-680 amino acid long extracellular amino terminal domain and an approximately 55 amino acid long cytoplasmic tail which contains intracellular trafficking signals. mRNA from the APP gene on chromosome 21 undergoes alternative splicing to yield eight possible isoforms, three of which (the 695, 751 and 770 amino acid isoforms) predominate in the brain. APP695 is the shortest of the three isoforms and is mainly produced in neurons. APP751 and APP770 are mostly found in non-neuronal glial cells. All these isoforms share the same Aβ, transmembrane and intracellular domains and are thus potentially amyloidogenic. Differential proteolysis of APP by enzymes known as secretases generates Aβ variants ranging in size from 39 to 43 amino acids, of which the 40-residue Aβ40 and 42-residue Aβ42 peptides are the most common (Hartmann et al., 1997; Zhang et al., 2011). Compared to Aβ40, Aβ42 is more prone to aggregation and more neurotoxic (Dahlgren et al., 2002). It is also seen that the ratio of Aβ42/Aβ40 is elevated in most of the familial AD cases. The normal function of APP is currently unknown but it has been demonstrated to be localized in synapses where