Pathogenic Mechanism of Alzheimer’s disease
The pathophysiology of Alzheimer’s disease is complex, involving several neurotransmitter systems and pathophysiologic process. The three hall marks of Alzheimer’s disease are the presence of neuritic (senile) plaques, neurofibrillary tangles, and amyloid angiopathy (Grossman & Porth, 2014). The neuritic plaques are patches or flat areas composed of clusters of degenerating nerve terminals arranged around a central amyloid core. The amyloid core has a dominant component called amyloid beta, a peptide derived from the proteolysis of a larger membrane-spanning amyloid precursor protein (APP). There are numerous studies that proved amyloid beta has an important role in the pathogenesis of Alzheimer’s …show more content…
This enzyme is required for the synthesis of acetylcholine, a neurotransmitter that is associated with the memory. The reduction in choline acetyltransferase is related to the numbers of neuritic plaques and severity of dementia (Grossman & Porth, 2014). In typical Alzheimer’s disease, the death of neurons in the nucleus basalis of Meynert leads to the deficit in acetyl choline. The mutations in three genes – the amyloid precursor protein gene on chromosome 21; presenilin-1, a gene on chromosome 14; and presenilin-2, a gene on chromosome 1 is also associated with Alzheimer’s disease in certain families (Grossman & Porth, 2014). Additional risk factors for Alzheimer’s disease include: head trauma, inflammatory factors, and oxidative stress. Abnormal cerebral serotonergic and adrenergic activity contributes to dysphoria and insomnia in Alzheimer’s …show more content…
The indirect-acting cholinergic agonists are the group of drugs that are prescribed for the treatment of Alzheimer’s disease. They work by reversibly blocking acetylcholinesterase at the synaptic cleft. This blocking allows the accumulation of ACh released from the nerve endings and leads to increased and prolonged stimulation of ACh receptor sites at all of the postsynaptic cholinergic sites (Karch, 2013). These indirect-acting cholinergic agonists cross the blood-brain barrier and mostly affect the cells in the cortex to increase ACh concentration in those areas of brain where the ACh-producing cells are dying. The indirect-acting cholinergic agonists that used for the treatment of Alzheimer’s disease include: donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), and tacrine (Cognex) (Karch, 2013). The drugs donepezil, rivastigmine, and galantamine inhibit acetylcholinesterase, preventing metabolism of endogenous acetylcholine, and are used in the early stages of the disease for mild cognitive impairment (Grossman & Porth, 2014). These drugs used for the treatment of Alzheimer’s disease are metabolized in the liver by the cytochrome P450 system, so these drugs should be used in caution with the patient with hepatic impairment (Karch, 2013). Tacrine is available in a capsule
The pathophysiology of Alzheimer’s disease is complex, involving several neurotransmitter systems and pathophysiologic process. The three hall marks of Alzheimer’s disease are the presence of neuritic (senile) plaques, neurofibrillary tangles, and amyloid angiopathy (Grossman & Porth, 2014). The neuritic plaques are patches or flat areas composed of clusters of degenerating nerve terminals arranged around a central amyloid core. The amyloid core has a dominant component called amyloid beta, a peptide derived from the proteolysis of a larger membrane-spanning amyloid precursor protein (APP). There are numerous studies that proved amyloid beta has an important role in the pathogenesis of Alzheimer’s …show more content…
This enzyme is required for the synthesis of acetylcholine, a neurotransmitter that is associated with the memory. The reduction in choline acetyltransferase is related to the numbers of neuritic plaques and severity of dementia (Grossman & Porth, 2014). In typical Alzheimer’s disease, the death of neurons in the nucleus basalis of Meynert leads to the deficit in acetyl choline. The mutations in three genes – the amyloid precursor protein gene on chromosome 21; presenilin-1, a gene on chromosome 14; and presenilin-2, a gene on chromosome 1 is also associated with Alzheimer’s disease in certain families (Grossman & Porth, 2014). Additional risk factors for Alzheimer’s disease include: head trauma, inflammatory factors, and oxidative stress. Abnormal cerebral serotonergic and adrenergic activity contributes to dysphoria and insomnia in Alzheimer’s …show more content…
The indirect-acting cholinergic agonists are the group of drugs that are prescribed for the treatment of Alzheimer’s disease. They work by reversibly blocking acetylcholinesterase at the synaptic cleft. This blocking allows the accumulation of ACh released from the nerve endings and leads to increased and prolonged stimulation of ACh receptor sites at all of the postsynaptic cholinergic sites (Karch, 2013). These indirect-acting cholinergic agonists cross the blood-brain barrier and mostly affect the cells in the cortex to increase ACh concentration in those areas of brain where the ACh-producing cells are dying. The indirect-acting cholinergic agonists that used for the treatment of Alzheimer’s disease include: donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), and tacrine (Cognex) (Karch, 2013). The drugs donepezil, rivastigmine, and galantamine inhibit acetylcholinesterase, preventing metabolism of endogenous acetylcholine, and are used in the early stages of the disease for mild cognitive impairment (Grossman & Porth, 2014). These drugs used for the treatment of Alzheimer’s disease are metabolized in the liver by the cytochrome P450 system, so these drugs should be used in caution with the patient with hepatic impairment (Karch, 2013). Tacrine is available in a capsule