Memory Systems

Question 1

what structures make up limbic system

Answer 1

medial temporal lobe with parts of diencephalon

hippocampus
anterior thalamic nuclei
amygdala
adjacent cortical areas (entorhinal cortex, perirhinal cortex, parahippocampal cortex)

Question 2

function limbic system

Answer 2

memory formation and emotional processing, esp fear

Question 3

hippocampus - memory function hypotheses

Answer 3

1. hippocampus stores incoming info and acts as temporary buffer ‘consolidating’ info and will pass info on to cortex for ultimate storage
2. long term memory is sorted in hippocampus which is essential for long term memory

available data supports hypothesis 1. but controversial. it is a network, deficit in any part will have an impact. doesn’t mean info is stored there, may just be needed to access info which is stored elsewhere

Question 4

declarative memory

Answer 4

(explicit)
included episodic and semantic memory

Question 5

non-declarative memory

Answer 5

(implicit)

habits and skills, implicit emotions

Question 6

episodic memory

Answer 6

individual experience related to past event
e.g. wedding

Question 7

semantic memory

Answer 7

meaning of something w/o remembering specific even where learnt it
e.g. know what a strawberry is but don’t know when learnt it

Question 8

Alzheimer’s end stage pathology

Answer 8

beta amyloid plaques
tau tangles
enlarged ventricles
inflammation
cortical atrophy

Question 9

Alzheimer’s characteristics

Answer 9

progressive cognitive decline

Question 10

Alzheimer’s: ABC score

Answer 10

A: amyloid deposition
B: break stage of neurofibrillary tau tangles
C: CREAD nutrition plaque score

Question 11

Alzheimer’s: genetic link

Answer 11

<1% cases purely genetic cause
linked to APP on Chr21 , familial mutations –> familial AD

(pt with trisomy 21 have extra chr21 –> APP on this chromosome)

Question 12

Alzheimer’s: genetic risk factors

Answer 12

apolipoprotein E

people with one cope APOE 4 are 3x more likely to be affected by AD

Question 13

AD pathophysiology: current key hypothesis

Answer 13

APP processing & b-amyloid plaque neurotoxicity
hyperphosphorylation of Tau
oxidative stress and ageing
diet and environmental factors (e.g. metals)
cholinergic signalling

Question 14

cholinergic hypothesis

Answer 14

reduced levels of ChAT (enzymes which generate ACh
loss of cholinergic neurons
affects target areas of cholinergic projections –> hippocampus and cortex (which are important for learning and memory)

currently only symptomatic treatment target

Question 15

formation of beta amyloid plaques

Answer 15

APP is transmembrane protein which is usually cleaves and produced by a growth factor - secretase APP alpha

in disease state, APP is cleaved by a different secreatase and produces beta amyloid protein which then forms plaques

Question 16

formation of tau tangles

Answer 16

oxidative stress and free radial formation –> disregulation of specific protein kinases –> hyperphosphorylation of tau

tau then comes away from the cytoskeleton and forms the tangles

Question 17

attempts to link amyloid and tau

Answer 17

amyloid dysregulates protein kinases –> tau hyperphosphorylation

but there is spatial paradox: tau and amyloid pathology do not start in same bits of brain
if one induces other they should start same area of brain

Question 18

amyloid hypothesis

Answer 18

proposed amyloid as cause of AD

Question 19

how does beta amyloid hypothesis not satisfy criteria for casual relationship with AD

Answer 19

dose response: you don’t get worse degree if more beta amyloid

temporal sequence: amyloid does not occur before see other damage

specificity: amyloid seen in other ND disease and in healthy people

Question 20

toxic protein propagation through brain

Answer 20

specific protein for each pathology

proposes that start with BA then tau comes in, then structural damage and oxidative stress. need sensitive detection for these

Question 21

AD risk factors

Answer 21

htn & CVS disease
sedentary, obesity, poor diet
alcohol
low levels cognitive engagement
stroke
smoking
depression
sleep disorders

Question 22

metal exposure as risk factor for AD

Answer 22

metals can induce tau hyperphosphorylation (high number of metal binding sites in tau proteins)

metals induce higher complex amyloid fibrils

Question 23

CNS metal physiology

Answer 23

Glut synapse - zinc co released with glutamate at high conc.

NMDA receptors have zinc binding site and depending on if this is occupied or not will have more/less calcium influx into post-synapse.

GABA receptors have metal binding sites. Will regulate excitation of nervous system - need good control over metal homeostasis

APP - number secreatases have copper and zinc binding sites which are essential for enzymes to work

beta-amyloid fragments have metal binding sites and when occupied get oligomers —> metal rich plaques

BA is cleared by enzyme which has zinc binding sites.