Alzheimer's Disease

Question 1

Not a disease itself but rather a group of symptoms that may accompany certain diseases or conditions

Answer 1

Dementia

Question 2

Irreversible when caused by disease or injury but may be reversible when caused by drugs, alcohol, hormone or vitamin imbalances, or depression

Answer 2

Dementia

Question 3

Often begn in pre-senescence

-Have both genetic and sporadic forms

Answer 3

Dementia syndromes

Question 4

Involve abnormal protein aggregation in neural tissue that disrupts neuronal function

Answer 4

Dementia syndromes

Question 5

Caused by mutations in genes that either code for or affect the function of a protein

Answer 5

Genetic forms fo dementia

Question 6

Characterized by the presence of neuritic plaques and tangles, as well as synaptic and neuronal loss due to apoptosis

Answer 6

Alzheimer’s Disease (AD)

Question 7

The most common age-related degenerative dementia, accounting for about 2/3 of all cases

Answer 7

AD

Question 8

Usually begins with the gradual failure of recent (episodic) memory–alertness and motor functions are spared

Answer 8

AD

Question 9

A clinical feature of AD that can also be reported as decreased taste

Answer 9

Anosmia

Question 10

A small percentage (~1%) have AD onset before age 60 (“pre-senile”). These typically are inherited, and are referred to as

Answer 10

Familial AD (FAD)

Question 11

Neuritic plaques contain extracellular deposits of insoluble fibrils composed of polymers of

Answer 11

Amyloid β-protein (Aβ)

Question 12

Exhibit dystrophic morphologies and tau tangles

Answer 12

Neurites

Question 13

Axons and dendrite trajectories are disrupted by

Answer 13

Neuritic plaques

Question 14

Gliosis and microglia induce

Answer 14

Oxidative stress/inflammation

Question 15

Arises from the normal processing of a longer transmembrane protein, Amyloid Precursor Protein (APP)

Answer 15

Amyloid β-protein

Question 16

What is the name of the enzyme that cleaves APP to creat beta amyloid proteins

Answer 16

BACE (Beta-site APP Cleavage Enzyme)

Question 17

Functions as a cell surface receptor/cell signaling or migration

-Also cell adhesion and neurite outgrowth and synaptogenesis

Answer 17

Amylolid Precursor Protein (APP)

Question 18

Post-mortem studies of AD patients have shown that neuritic plaques are composed primarily of the

Answer 18

42aa form of Aβ protein

Question 19

Extracellular accumulation of insoluble Aβ-42 disrupts neuronal and synaptic function, leading to cell death, and is the causative factor for

Answer 19

AD

Question 20

Amyloid plaques and neurofibrillary tangles form in mice over-expressing* mutant forms of

Answer 20

Human APP and Tau

Question 21

Is present in extracellular plaques in transgenic mice that over-express both proteins (i.e., this form is more prone to aggregate)
Mouse

Answer 21

Aβ-42 but not Aβ-40

Question 22

Adults with Down (Trisomy 21) develop early onset AD (~age 40). This is correlated to increased

Answer 22

APP gene dosage/Aβ-42 production

Question 23

To date, the only mutations known to cause dominantly inherited AD result in an excessive production/deposition of

Answer 23

Aβ-42

Question 24

Lead to abnormal processing and, most commonly, increased production of Aβ-42 peptide

Answer 24

Missense mutations within the APP gene

Question 25

These mutations account for <0.1% of the AD cases

Answer 25

APP missense mutations

Question 26

A673T substitution reduces formation of Aβ by

Answer 26

40%

Question 27

A 34kD glycoprotein that is involved in cholesterol and lipids transport and may normally be involved in cell membrane repair

Answer 27

ApoE

Question 28

Inheritance of which ApoE increases the risk of developing AD (by 3-15 fold), -Although it is neither sufficient nor required for disease development

Answer 28

Inheritance of ApoE4

Question 29

Produces a protein that is less stable than the other alleles

Answer 29

ApoE4

Question 30

Impairs Aβ-42 clearance, promoting aggregation -Promotes tau hyperphosphorylation

Answer 30

ApoE4

Question 31

Similar to ApoE4 -Regulates Aβ-42 aggregation, deposition

Answer 31

Clusterin/Apolipoprotein J

Question 32

Complement related protein that may play a role in Aβ-42 clearance

Answer 32

CR1

Question 33

Involved in endocytosis -May regulate APP trafficking in cells

Answer 33

PICALM

Question 34

Part of the gamma-secretase protein complex that produces Aβ-42 from APP

Answer 34

Presenilin Proteins (PS1, PS2)

Question 35

Gain of Function Mutations in Presenilin Genes are Associated with

Answer 35

FAD

Question 36

Mice with mutations in PS1 (that likely increases its stability or activity) show accelerated

Answer 36

Amyloid deposits

Question 37

Reduction in plaque load by antibody immunotherapy in humans does not improve

Answer 37

Memory Function

Question 38

Bind to specific neuronal receptors, which can result in cell death

Answer 38

Aβ oligomers

Question 39

Aβ oligomers bind to specific neuronal receptors including:

Answer 39

PrPc, EphB2, Fcy-RIIb, and LilrB2

Question 40

Expressed in the immune system and by neurons on growth cones and synapses

Answer 40

LilrB2 (leukocyte immunoglobulin-like receptor B2)

Question 41

Activation of signaling with Aβ oligomers triggers

Answer 41

Actin cytoskeletal disruption and synaptic loss

Question 42

Transgenic AD mice (APP/PS1) also lacking the mouse ortholog (PirB) are protected against

Answer 42

Neuronal damage and memory deficits

Question 43

Contain intracellular deposits of hyperphosphorylated tau (microtubule-associated) protein

Answer 43

Neurofibrillary tangles

Question 44

Important structural elements in neurons that are involved in cell/axon integrity and transport

Answer 44

Microtubules

Question 45

Abnormal phosphorylation renders tau less soluble and more prone to form -impairs axonal transport of cargo

Answer 45

Filamentous aggregates

Question 46

The gene encoding tau is not genetically linked to AD, but it is linked to

Answer 46

Frontotemporal dementia

Question 47

What are the serum levels of Aβ-42 and Tau that suggest a patient is more likely to develop AD?

Answer 47

Low [Aβ-42] and high [tau]

Question 48

Stages of AD involving the entorhial and hippocampal cortex

Answer 48

Stages I-II

Question 49

The main input into the hippocampus and is responsible for pre-processing (familiarity) input signals

Answer 49

Entorhinal cortex

Question 50

One of the first symptoms of AD is

Answer 50

Impaired sense of direction and object recognition

Question 51

Involves the adjoining high order association areas of the basal temporal neocortex

Answer 51

Stages III-IV

Question 52

Involves additional neocortical association areas, eventually extends into the primary areas of the neocortex

Answer 52

Stges V-VI

Question 53

Language and cognition are profoundly effected in stages

Answer 53

V-VI

Question 54

Current pharmaceutical treatment strategies involves which 2 types of drugs?

Answer 54

Acetylcholinesterase inhibitors and NMDA antagonists

Question 55

May protect the brain from glutamate excitotoxicity

Answer 55

NMDA antagonist (Namenda)

Question 56

Physical exercise (elevation of heart rate for at least 30 minutes several times a week) may currently be the most effective therapy to prevent or offset

Answer 56

AD

Question 57

Projection neurons that have long, un- or sparsely-myelinated axons appear to be particularly susceptible to

Answer 57

AD

Question 58

Areas of the brain that are the most severely affected with AD appear to be involved in

Answer 58

Processing

Question 59

This idea correlates with studies showing that education, which directs waking brain activity away from default-mode to task-specific brain networks, may delay

Answer 59

AD onset