1. 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

2. Microscopy of the aging brain
Increase in lipofuscin
Senile plaques
Neurofibrillary tangles
Granulovacuolar degeneration
Hirano bodies
Leukoaraiosis
Amyloid (congophilic) angiopathy

3. 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

4. Ubiquinopathies: Alzheimer’s disease
Pre-senile and senile forms
Onset before or after 65 years of age
Progression slow (often > 1 decade)
Pathological changes are similar to aging, but more severe

8. 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

14. Tauopathies Pick’s disease Progressive Supranuclear Palsy
Cortico basal degeneration
etc

15. Pick’s 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)
Histology:Pick’s cells (swollen neurons ), Pick’s bodies ( argyrophilic intracytoplasmic inclusions), neuronal loss and gliosis

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

24. Synucleinopathies
Parkinson’s disease
Dementia with Lewy bodies
etc

25. 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

26. Parkinson’s disease

27. Lewy bodies

28. Synuclein

29. Dementia with Lewy bodies