Physiology - Research Paper Example

Your Human Physiology 15 April Clinical and Biomarker Changes in Dominantly Inherited Alzheimer’s Disease Alzheimer’s disease is the most common cause of dementia in the elderly. Brain pathological changes include deposition of amyloid-beta and tau proteins in and around neurons, leading to neuronal death. The disease process and histological changes in the brain are postulated to begin several years before the disease is actually apparent. In a subset of patients, it is associated with genetics and an autosomal dominant inheritance.

The researchers Bates et al. studied the natural history of pathological changes of autosomal-dominant Alzheimer’s disease, by studying carriers of the mutation before they developed the disease. The researchers selected 128 children of patients with autosomal-dominant Alzheimer’s disease as study participants, as they were at risk of carrying the mutation. The autosomal-dominant nature of the disease in these cases was determined by family pedigrees. The mutations known in these pedigrees included presenilin 1, presenilin 2, and amyloid precursor protein.

The expected age of symptom onset for the participants was set as the age at which the parent was diagnosed with Alzheimer’s disease. They studied several physiologic mechanisms occurring in these patients. First, they carried out clinical assessments of cognitive change using questionnaire-based scales, giving them a cognition score. This characterized the participants as normal cognitive function, very mild impairment, or mild impairment. Brain imaging with magnetic resonance imaging (MRI) was done to screen for any pre-existing brain disease.

Positron emission tomography (PET) scanning was done to determine any regions of fibrillar amyloid deposition, and decreased metabolism. They also analyzed cerebrospinal fluid (CSF) for concentrations of tau, and beta-amyloid. They found that 50% of the asymptomatic study participants were carriers of the mutation for Alzheimer’s. The carriers had lower cognitive scores and at an earlier age, compared to non-carriers of the mutation. The carriers also developed bilateral hippocampal atrophy, seen on MRI, 15 years before expected symptom onset.

Through PE scanning, they detected a selective decrease in the metabolism of the precuneus region of the brain in carriers, 10 years before expected symptom onset. Mutation carriers also had significant amyloid deposition in the precuneus region at 15 years before symptom onset, while non-carriers did not have any amyloid deposition there. Levels of CSF tau protein and plasma amyloid were elevated in the carriers 15 years before symptom onset, compared to non-carriers. Using combined statistical models, they determined that beta-amyloid deposition, increased tau levels in the brain, and cortical atrophy begin about 15 years before onset of symptoms in autosomal-dominant Alzheimer’s disease.

Cerebral hypometabolism and impaired memory develop about 10 years before symptom onset in Alzheimer’s, and global cognitive impairment starts at 5 years before symptom onset. The mechanisms studied by these researchers were the changes in histological and physiological protein levels, as well as structural changes in the brain in autosomal-dominant Alzheimer’s disease. They used clinical, neurophysiological, imaging and biochemical investigations, as well as statistical models for comparisons, to obtain information on the natural history of these changes.

The linear mixed model and Approximate Student’s t-test were used for statistical analysis. There are several new things I learned from this paper. First, that the mutations in genetics of Alzheimer’s are presenilin 1, presenilin 2, and amyloid precursor protein. I also learned that the brain pathological changes begin several years before Alzheimer’s becomes clinically apparent. I learned what abnormalities occur in the brain in Alzheimer’s –how the impaired memory in Alzheimer’s is linked to atrophy of the hippocampus, as well as how cognitive decline in Alzheimer’s is linked to diffuse cortical atrophy.

I learned that reduced brain metabolism is also an indication of dementia. I learned that the first detectable changes in those at risk of developing Alzheimer’s by genetic inheritance, appear 15 years before symptom onset. I also learned that this information can be used to arrest these pathological changes in Alzheimer’s in asymptomatic carriers, so that they can be prevented from developing Alzheimer’s disease. Work CitedBateman, Randall J., et al. "Clinical and biomarker changes in dominantly inherited Alzheimers disease.

" New England Journal of Medicine 367.9 (2012): 795-804.