Alzheimer's Disease

what markers are used for AD?

Amyloid plaques - ABeta1242 Neurofibillary tangles - P-tau

what parts of the brain degenerate first in early AD?

hippocampus and amygdala

describe Alzheimer's pathophysiology.

•*Neuritic plaques* -extracellular - abnormal insoluble amyloid protein fragments •*Neurofibrillary tangles* - intracellular - disturbed tau-microtubule complexes (hyperphosphorylated tau) -causes accumulation of proteins and cell dies •Cholinergic system degeneration with significant loss of neurons in certain areas (such as Nucleus Basalis of Meynert) •Degeneration often begins in *enterorhinal cortex* and progresses to other limbic structures

what is the pathological process of AD?

•AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus. •*Plaques are dense, mostly insoluble deposits of amyloid* - beta peptides and cellular material outside and around neurons. •*neurofibrillary tangles* are aggregates of the microtubule-associated *protein tau* which has become hyperphosphorylated and accumulate inside the cells themselves. •Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of AD patients have a greater number of them in specific brain regions such as the temporal lobe. •AD has been identified as a protein misfolding disease , caused by accumulation of abnormally folded A-beta and tau proteins in the brain. Plaques are made up of small peptides, 39-43 amino acids in length, called beta-amyloid. •Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP) •AD is also considered a tauopathy due to abnormal aggregation of the tau protein. •In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron's transport system.

what are the behavioral problems seen in AD pts?

•Almost universally a problem at some point •*60% of AD at any one time exhibiting significant sxs (usually delusions and/or agitation)* •Common problems by order of prevalence: -agitation -depression -delusions/psychosis •Additional behavioral problems -disinhibition, apathy, personality change, anxiety, wandering, insomnia

what changes are caused by AD?

•Diminished blood flow -why brain shrinking, not getting enough nutrients •*Neurofibrillary Tangles* -pathologic marker •*Neuritic Plaques* -pathologic marker -accumulate in the brain •Degeneration of hippocampus, cerebral cortex, hypothalamus, and brain stem -*hippocampus very sensitive to early AD*

describe the general drug tx in AD.

•Many drugs aim to stimulate the cholinergic system •These drugs have limited positive effects and do not reverse the causes of AD •*No effective tx right now*

what are the sxs of mild cognitive impairment of AD?

•getting lost •trouble handling money and paying bills •repeating questions •taking longer to complete normal daily tasks •poor judgment •losing things or misplacing them in odd places •mood and personality changes

what are the sxs of severe stage of AD?

•inability to communicate •weight loss •seizures •skin infections •difficulty swallowing •groaning, moaning, or grunting •increased sleeping •lack of control of bowel and bladder

what are the sxs of moderate stage of AD?

•increased memory loss and confusion •problems recognizing family and friends •inability to learn new things •difficulty carrying out tasks that involve multiple steps (such as getting dressed) •problems coping with new situations •hallucinations, delusions, and paranoia •impulsive behavior