The ageing brain

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The ageing brain

• Volume reduction begins around 50 with a loss
  of brain weight of around 2-3 per decade
• Changes in nerve cell numbers and size
• - various studies with various results (
  10-25), although some structures seem resistent
• - dendritic and synaptic changes may be
  compensated by sprouting

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Microscopy of the aging brain

• Increase in lipofuscin
• Senile plaques
• Neurofibrillary tangles
• Granulovacuolar degeneration
• Hirano bodies
• Leukoaraiosis
• Amyloid (congophilic) angiopathy

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Neurodegenerations

• Damage to lysosomes, nuclear DNA, mitochondria
  leads to release of caspases, initiating
  apoptosis.
• In many if not most neurodegenerations this
  damage is started by abnormal protein-protein
  interactions leading to protein storage.
• Examples
• Ubiquinopathies
• Tauopathies
• Synucleinopathies
• Prion diseases

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Ubiquinopathies Alzheimers disease

• Pre-senile and senile forms
• Onset before or after 65 years of age
• Progression slow (often gt 1 decade)
• Pathological changes are similar to aging, but
  more severe

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Senile plaque

• Heterogeneous structure
• Amyloid core surrounded by a clear zone
• Crown of filamentous or granular material
• made up of neuronal projections filled with
• argyrophilic filaments and debris
• Macrophages and astrocytes

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Tauopathies

• Picks disease
• Progressive Supranuclear Palsy
• Cortico basal degeneration
• etc

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Picks disease

• Dementia with relative rapid progression with
  frontal symptoms (aggressive behavior often, or
  problems with initiation of tasks), onset from 50
  years of age, frequently hereditary.
• Gross findings are characterized by a lobar
  atrophy affecting the frontal lobe and the
  anterior temporal lobe (mostly the anterior 1/3
  of the superior temporal gyrus)
• HistologyPicks cells (swollen neurons ), Picks
  bodies ( argyrophilic intracytoplasmic
  inclusions), neuronal loss and gliosis

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Progressive supranuclear palsy

• Dementia combined with vertical gaze paralysis,
  and Parkinsonism
• Abnormal tau accumulation in neurons and glial
  cells, neuronal loss and gliosis
• Characteristic topographyIn the midbrain and
  striatum (Substantia nigra, red nucleus,
  colliculi, globus pallidus, subthalamic nucleus,
  periaqueductal grey matter, dorsal and medial
  raphe, locus coeruleus)

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Synucleinopathies

• Parkinsons disease
• Dementia with Lewy bodies
• etc

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M. Parkinson

• Onset 30-80
• Rest tremor mostly starting with hands (like
  counting money)
• Stooped posture, walking with small steps
• Depigmentation of Substantia nigra and Locus
  coeruleus
• Lewy bodies and loss of pigmented neurons
• Loss of dopaminergic innervation to the striatum

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Parkinsons disease
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Lewy bodies
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Synuclein
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Dementia with Lewy bodies