Tauopathies

Question 1

what lobes are affected in AD?

Answer 1

temporal (41%) –> greatest weight loss
parietal (30%)
frontal (14%) –> greatest amount of atrophy

Question 2

what grossly happens to the brain w/ AD?

Answer 2

decreased thickness of cortical ribbon 
ventricular dilation 
size difference 
gyri thinner
sulci wider 
discoloration

Question 3

what neurons and their NTs are lost in AD?

Answer 3

basal forebrain (nucleus basalis of Meynert) –> ACh
Locus Ceruleus –> NE
Dorsal Raphe Nuclei –> 5-HT (serotonin)

Question 4

what are plaques?

Answer 4

beta-amyloid deposited outside of the cell that does not DO anything

Question 5

what are neurofibrillary tangles?

Answer 5

polymerized taus found IN the neurons

Question 6

what is APP?

Answer 6

Amyloid precursor protein (APP) is a normal transmembrane glycoprotein 695 residue peptide of unknown function. Can form a-beta plaques in AD w/ the wrong secretase (beta + gamma)

Question 7

what is Aß protein?

Answer 7

Aß protein is a 42/43-residue peptide that is found in the membranous and extracellular part of the APP, cleaved by β and γ secretase, and causes AD.

normal = A 39/40 residue Aβ is found in CSF of normal patients and formed by α and γ secretase.

Question 8

what is Amyloid Angiopathy?

Answer 8

Normally no amyloid in BV
Tauopathies amyloid is stored in BV –> makes BVs brittle –> rupture –> amyloid angiopathy

congo stain

• LM –> amyloid –> pink
• fluorescence –> amyloid –> green

Side Feature Seen with Tauopathies

Question 9

what are Hirano Bodies?

Answer 9

Polymerization of proteins not functioning properly

Side Feature Seen with Tauopathies

Question 10

what is granulovascular degeneration?

Answer 10

Sphere with dots in them
neuron with mutated tau tried to get rid of abnormal tau in organelles (ex. lysosomes)
Side Feature Seen with Tauopathies

Question 11

genes for early onset AD? How old are they when they are demented?

Answer 11

Amyloid precursor protein (APP) gene missense mutation (12 different mutations), account for 0.1% of AD

PSEN1 gene mutation (>100 mutations), 50% of cases

PSEN2 gene mutation (7 mutations)

demented at 50yo

Question 12

genes for late onset AD?

Answer 12

Apolipoprotein E 4

Question 13

why do down’s patients get AD? How old are they whey they get it?

Answer 13

Three APP genes, increased production of APP
iMultiple mutations in APP gene:

have Alzheimer’s and demented by 30yo

Question 14

Corticobasal Degeneration causes atrophy of what? When do symptoms begin?

Answer 14

cerebral cortex

basal ganglia –> movement disorder

Question 15

Corticobasal Degeneration: When do symptoms begin? what do you see microscopically?

Answer 15

60yo
unilateral first –> then bilateral
Extracellular plaques + neurofibrillary ganglia

Question 16

Pick’s Disease: what is the order of lobes hit?

Answer 16

Fronto-temporal atrophy Dementia

Frontal –> then temporal

Question 17

Personality + Short Term Memory Changes

Answer 17

pick’s disease

Question 18

knife-edge

Answer 18

pick’s disease

Question 19

Pick’s bodies

Answer 19

limbic and paralimbic cortices, ventral temporal lobe; dentate granule cells and the pyramidal cell layer of the HIPPOTHALAMUS

Question 20

Microvascular Degeneration

Answer 20

do NOT have Alzheimer’s
may be demented
have had STROKES or HIGH BP –> Physician tries to normalize –> mini-strokes in the brain

Question 21

macroscopic presentation of Microvascular Degeneration

Answer 21

Brains WILL be atrophic, narrow gaps

will NOT have plaques or tangles

Question 22

microscopic presentation of Microvascular Degeneration

Answer 22

pin-point hemorrhages