Alzheimer Disease 1.

Is The Most Common Cause Of Dementia In The Elderly With Cerebrovascular Disease & Several Less Common Neurodegenerative Diseases Accounting For The Rest Of The Dementias 2. Most Occur After Age 50 With Progressive Increase In Incidence With Advancing Age. 3. Factors Which Play A Role In The Development Of The Disorder: Genetic Factors: A. The Occurrence Of Familial Cases B. At Least 4 Genetic Loci Linked To Familial Alzheimers Disease C. Chromosome 21 Encodes For A Protein Known As Amyloid Precursor Protein (APP). As We Will See APP Is The Source Of Amyloid Deposits In A Variety Of Sites In The Brain Of AD Patients D. Mutations In Two Additional Genes Termed Presenilin 1 & Presenilin 2 Located On Chromosomes 14 and 1 Account For A Much Larger Proportion Of Familial AD Especially Those At Early Onset AD. Mutations In These Genes Associated With Increased CNS Amyloid . E. An Additional Group Of Cases Of Late Onset Familial AD Is Linked To Expression Of The Epsilon-4-Allele Of Apolipoprotein E Encoded On Chromosome 19.

F. Deposition Of A Form Of Amyloid Derived From The Breakdown Of APP Is A Consistent Feature Of AD. The Breakdown Product Beta- Amyloid is a Prominent Component of the Senile Plaques Found In The Brains Of Alzheimer Patients & Is Present Within The Walls Of Cerebral Blood Vessels As Well. G. There Are 3 Enzymes Involved In The Process Of Amyloid Deposition They Are Alpha, Beta & Gamma Secretases. It Appears That BetaAmyloid Is The Major Component Of The Amyloid Plaque. H. Cytoskeletal Abnormalities In AD: Tau Is An Intracellular Protein That Is Involved In The Assembly Of Intra- Axonal Microtubules. In AD There Is Hyperphosphorylation Of The Tau Protein Which May Interfere With The Maintainance Of The Normal Microtubules Of The Neuronal Cells. I. In Murine Models Of Alzheimer Disease: The APP Or Its Product : Beta Amyloid Increases The Formation Of Neurofibrillary Tangles Derived From Tau Proteins. J. The Apoprotein E Molecule Containing The Epsilon-4-Allele As Well Is Reported To Bond Beta-Amyloid Better Than Other Forms Of Apoprotein E & May Contribute To Enhanced Amyloid Fibril Formation

10. The Histopathology Of Alzheimer Disease (In Summary) 1. Neurofibrillary Tangles: The Major Component Of Which Is Hyperphosphorylated Tau Protein 2. Senile Plaques: Contain Beta Amyloid 11. Clinical Features: A. Progressive Impairment Of Memory & Other Cognitive Functions B. Progresses To Complete Disorientation C. Loss Of Language D. Loss Of Higher Cortical Brain Function E. Death Usually Results From Intercurrent Bronchopneumonia Or Other Infections 12. Rx: A. Acetylcholinesterase Inhibitors: 1. Tacrine (Cognex) : Side Effects: Liver Damage 2. Donepizil (Aricept) 3. Galantamine (Reminyl) 4. Rivastigmine (Exelon) B. N-Methyl-D-Aspartate Receptor Antagonist 1. Memantine (Namenda) C. For: Anxiety: 1. Buspirone D. For Aggression & Agitation: 1. Haloperidol 2. Risperidone 3. Olanzapine 4. Quetiapine

E. Clinical Trials: 1. Flurizan 2. Alzhemed 3. Vitamin E 4. Bapineuzumab Removes Beta Amyloid Peptides 5. Docosahexanoic Acid (DHA) 6. IV Immunoglobulin 7. LY-450139: Gamma Secretase Inhibitor A. Gamma Secretase: Plays Key Role In Amyloid Production 8. Rosiglitazone A. May Increase Sensitivity of Insulin & Make Glucose More Available To The Brain