Thought to only apply to individuals under 65 years of age, and to be rare.

The patient was young so they thought it affect individuals under the age of 65 Definite Diagnosis Examination of brain tissue to determine prevalence of neuritic plaques and neurofibrillary tangles (Pathalogical Halmarks) Clinical Criteria Identify presence of syndrome Decline in cognition from previous higher level Imparies two or more domains of cognition Identify etiology in order to rule out other possible causes of impairment. Progression of cognitive decline is gradual Cognitive Patterns in AD Difficult learning and retaining new information (episodic memory) Characteristic of the disease is a decrease in the number of Acetylcholine neurotranmister (Ach is important for memory) One current way to treat is by giving Cholinesterase Inhibitors Plaques are composed of Amaloyd (Abeta) Plaques are outside nerve cells Tangles are made of protein called Tau Genetic There are three mutations that cause Alzhimers Chromosome 21 (APP Gene : Amyloid Precursor Protein) o People with Downs Syndrome have plaques and tangles, might not be demented but have the pathology Chromosome 14 (PS1 Gene) Chromosome 1 (PS2 Gene) o PS1/PS2 code for Gamma-Secretase Experiments making animal models with the mutations on the genes showed an increase in Abeta 42 to Abeta 40 ratio Late onset is usually due to mutation of Chromosome 19 (APOE Gene) APOE4 Allell increases susceptibility to get AD First thing that happens when you get disease is increase in production of Amloyid Beta, When that gets prominent enough to form neuritic plaques that accelerates the formation of tangles and then when there are enough of both that start to cause synaptics alteration and eventually the death of neurosynapses. Medication is focusing on Anti Amylodi aggregation Gama Secretase &Beta secreatase clips the proteins that produce Amyloid

Companies are looking for inhibitors of these in order to slow down the formation of amyloid o Vaccine against abnormal amyloid to remove or break it down. Anti Tau aggregation

Enterinal Cortex, and Hippocampus are affected areas. Drugs that failed might work on MCI. More effective when given before wide spread neuronal loss Biomarker is a biological substance that is present that is related to underlying pathology and that you can track. Amyloid Tau (measure indirectly by neuronal injury [look at changes in hippocampal volume, or changes in perfusions] as a result of tau) Measuring Amyloid and tau in cerebro spinal fluid because you can do it reliably PREVIOUS EXAM QUESTIONS 1. What are the cardinal pathological signs of AD in a post-mortem brain? Be sure to indicate the chemical make-up of these pathological entities and whether they exist in cytoplasm or extracellular space a. Amyloid Plaques (filled with ABeta42) and neurofibrillary tangles (filled with hyperphosphorylated tau). The plaques are extracellular and the tangles cytoplasmic. 2. What biological or biochemical tests can reinforce the conclusion that a person is suffering from Alzheimers disease? a. Spinal Tap to measure the Tau/Abets42 ratio the higher the ratio the more likely a diagnosis for Alzheimers. 3. Genetic screens of people who suffer from early onset Alzheimers disease identified three mutated genes on separate chromosomes. In what way are the proteins coded by these genes similar? a. Each increases the ratio of Abeata42 to Abeta40 4. In doing a cognitive evaluation of a patient you suspect of Alzheimers disease what are the deficits you are looking for? a. Difficulty in learning and retaining new information and deficits in executive functions that progress over time. 5. What clinical features do physicians look for to rule in AD? a. There must be a progressive decline from a previous higher level in two domains of cognition, such as memory and language. 6. What must a physician rule out to make a preliminary determination of AD? a. Other causes of dementia include infections, metabolic disorders and trauma. 7. Dr. Albert told us one of the major figures in the study of AD calls it, without hesitation, an overproduction of Amyoid. What are the datathat make him so certain AD is caused by an overproduction of amyloid? a. Familial AD is drven by mutations in genes that code for proteins critical in the formation of toxic amyloid Beta protein (Abeta42). Animal models of AD that target

those same genes replicate the symptoms of AD(memory decline, plaque and tangle formation) and treatments that inhibit production of Abeta42 stops those symptoms in the animal models. SIDE NOTES Amyloid aggregation is extracellular Tau aggregation is cytoplasmic