The Ageing Brain

Question 1

What determines the number of cell divisions of brain tissue? Do more cells grow throughout life?

Answer 1

Shortening of telomeres, although there is a slow neurogenesis in the adult brain

Question 2

What happens to the DNA throughout the lifespan?

Answer 2

It accumulates spontaneous mutations, which increase the errors in proteins and ultimately affects organ systems

Question 3

What causes DNA damage?

Answer 3

ROS, toxic environmental factors, alterations in hormones / growth factors

Question 4

What cognitive declines occur in the ageing brain?

Answer 4

1. Memory loss, related to synapse loss in entorhinal + hippocampus
2. Delayed memory retrieval of short-term
3. Declines in processing speed + learning
4. Reduced spatial memory
5. Altered executive function - reduced and slow decision making

Question 5

What are the age-stable cognitive functions?

Answer 5

Long-term memory, attention span, vocabulary, and verbal knowledge

Also, emotional stability increases with age

Question 6

How much brain weight is lost by age 80? What cell population is more affected?

Answer 6

average of 15%, Lost of neurons and oligodendrocytes rather than astrocytes / microglia (white matter density reduction in prefrontal cortex + anterior corpus callosum)

Question 7

What areas of the brain are prominently affected in aging?

Answer 7

Prefrontal cortex, medial temporal gyri, dentate gyrus, all involved in executive function and memory

Brainstem locus ceruleus and SNc loss, leading to movement, balance, and postural dysfunctions in elderly.

Question 8

What is dendrite plasticity and how long is it preserved?

Answer 8

Ability loss of dendrites to be compensated by gain of other dendrites to maintain stability of receptor surfaces for new synapses.

Beyond age 80, there are net losses of dendrites, which underly cognitive decline

Question 9

What is synaptic plasticity?

Answer 9

The capability of synapses to adapt or be replaced in response to changes in their environment -> single most important mechanism for maintaining critical brain function during aging

Question 10

What two cell types play a major role in synaptic remodeling during plasticity?

Answer 10

Microglia and astrocytes -> act as phagocytic cells for the dead synapses, and guide new ones to be formed

Question 11

What neurotransmitters are most vs least affected in aging?

Answer 11

Catecholamines most affected, GABA /glycine least affected

Question 12

How does Ca+2 homeostasis play into aging?

Answer 12

Decreased ability to buffer Ca+2 intracellular leads to excitotoxicity and subsequent activation of proteases whic degrade intracellular organelles + cell membrane

Question 13

What genes are upregulated during aging?

Answer 13

Genes involved in the stress response, including antioxidant defense i.e. superoxide dismutase and glutathione reductase

Question 14

What genes are downregulated during aging?

Answer 14

Genes involved in synaptic functions for memory + learning, genes involved in axonal transport and mitochondrial function

Question 15

What is the incidence of Alzheimer’s disease? What is the prognosis

Answer 15

Affects 50% of people over age of 85 years - mean survival after diagnosis is 6 years

Question 16

What are the three hallmarks of Alzheimer’s disease?

Do these occur normally?

Answer 16

1. Nerve cell loss
2. Neurofibrillary tangles
3. Senile plaques

These all occur normally, but much faster in AD

Question 17

What are the most significantly affected lobes in AD?

Answer 17

Frontal, parietal, and temporal

-> sensory and motor cortices are less affected, as well as the occipital cortex

Question 18

What subcortical centers are significantly affected in AD?

Answer 18

Amygdala, nucleus basalis of Meynert, locus ceruleus, and dorsal raphe

Question 19

How are neurofibrillary tangles formed? What are they linked to?

Answer 19

A component of the microtubule, tau protein, becomes hyperphosphorylated and links into filaments called tangles. These are linked to dementia as they disrupt axonal transport, and lead to improper delivery of proteins

Question 20

Where do senile plaques mostly accrue in Alzheimer’s?

Answer 20

Entorhinal cortex and hippocampus

Question 21

What proteins predispose you for familial AD?

Answer 21

Presenilin 1 and presenilin 2

Question 22

What amyloid precursor protein abberant cleavage leads to formation of senile plaques?

Answer 22

gamma-secretase. Alpha and beta will lead to normal protein formation.

Question 23

What is the first line therapy of the early stages of Alzheimer’s disease?

Answer 23

Cholinesterase inhibitors

Question 24

What is helpful in the late stages of Alzheimer’s?

Answer 24

Glutamate NMDA receptor antagonist (prevents excitotoxicity)

Question 25

What is the newest treatment for Alzheimer’s disease currently in trials?

Answer 25

Monoclonal antibodies which binds the amyloid plaques, slows cognitive decline but is associated with headaches