NE102 Lecture Notes 3

Mild cognitive impairment mci signs of impaired short

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Mild cognitive impairment (MCI) Signs of impaired short-term memory; Generally self-sufficient Mild AD Clearly impaired short-term memory Moderate
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Fundamentals of Alzheimer’s Disease (AD) 18:04 Needs regular help with daily living Severe Near inability to remember, communicate, or process information MACROSCOPIC FEATURES MICROSCOPIC FEATURES  Alois Alzheimer  Key patient; Auguste Deter Alzheimer performed postmortem histology on Deter’s brain to determine if microscopic  lesions or other abnormalities were present. Histology:  the study of microscopic structures/features of tissues Key steps: Tissue is sliced into extremely thin slices Tissues slice is mounted and fixed onto a glass slide Tissues is stained with dyes to bind tissue structures for microscopic imaging. Numerous stains have been generated and are now used routinely to visualize  microscopic features.  Alzheimer ID’d two key abnormalities: (1) Intracellular deposits = tangles Accumulated material inside the cell bodies of neurons Tangles:  aggregates of paired helical filaments (aka PHFs)
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Fundamentals of Alzheimer’s Disease (AD) 18:04 Referred to as  neurofibrillary tangle (aka NFTs) (2) Extracellular deposits = plaques Aggregated material outside of cells within the parenchyma Plaques:  Protein aggregates form amyloid structure.  Referred to as  amyloid plaques deposits.  Neurodegeneration (early 1980’s) ~ 50% fewer neurons in brains of Alzheimer’s patients Spine and synapse loss Dendrites form synapses through  dendritic spines Spines grow and shrink during LTP Decreased spine density Obvious hypothesis: Tangles and/or plaques
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Finding the Molecular Cause of Alzheimer Disease 18:04 Several new questions: What are tangles and plaques? How do they form? Why do they form in AD brain? i.e., what regulates their function? How do tangles and plaques affect neuronal function and health? AMYLOID PLAQUES Plaques are predominantly composed of a single peptide: amyloid-  (A ) β β AB exists in brain predominantly in two forms: A  40 and A  42 β β QUESTION: Why was this discovery so important to advance research on AD? Researchers could now generate anti- A  antibodies to study A .
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Mild cognitive impairment MCI Signs of impaired short term...

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