Download Learning Objectives of Degenerative Diseases - By : Prof Dr

• Degenerative Diseases
• Semester VIII
• Prof Dr Syed Mehmood Hasan
• Pathology Department SMC
• Degenerative Diseases
• Progressive and selective loss of functional neuronal system
• They can be grouped using two approaches:
•
Symptomatic/anatomic: based on the anatomic regions of the CNS that are
primarily affected, reflected in the clinical symptoms
• Pathologic: based on the types of inclusions or abnormal structures observed
• The pattern of neuronal loss is selective
• One or more groups of neurons are affected while leaving others situated
immediately adjacent to thios remains intact.
Degenerative diseases affecting:
• Cerebral cortex:
Alzheimer’s disease
Fronto-temporal dementias
Pick disease
Progressive supra nuclear palsy
• Basal Ganglia and brainstem:
Parkinson's disease
Huntington's disease
• Motor neurons:
Amylotrophic lateral sclerosis
Bulbospinal atrophy
Spinal muscle atrophy
• Alzheimer Disease
• Most common cause of dementia in elderly
• Impairment of high intellectual functions
• Mood + behavior alteration
• Memory loss
• Aphasia
• Progressive disorientation
In 5 -10 years, the patient becomes:
• Profoundly disabled
• Mute
• Immobile.
• Patients rarely become symptomatic before 50 years of age
• Clinical Features
• The progression of AD is slow but persistent
• A symptomatic course often running more than 10 years.
Initial symptoms:
1. Forgetfulness
2. Memory disturbances
3. Language deficits
4. Loss of mathematical skills
5. Loss of learned motor skills.
Final stages of AD:
1. Incontinent
2. Mute
3. Unable to walk.
Intercurrent disease:
• Morphology
Gross:
• Compensatory ventricular enlargement (hydrocephalus ex vacuo) secondary
to loss of parenchyma
• Reduced brain volume.
• Structures of the medial temporal lobe, including hippocampus, entorhinal
cortex and amygdala, are involved early in the course and are usually severely
atrophied in the later stages.
Microscopic Hallmarks:
• The major microscopic abnormalities of AD, which form the basis of the
histologic diagnosis
– Neuritic plaques
– Neurofibrillary tangles.
• There is progressive and eventually severe neuronal loss
• Reactive gliosis in the same regions that bear the burden of plaques and
tangles
Neuritic plaques :
• Focal
• Spherical collections of dilated, tortuous, neuritic processes
• Around a central amyloid core
• Surrounded by clear halo
• Neuro-fibrillary tangles
• These are bundles of filaments in neuronal cytoplasm that displace or encircle
the neurons
• These are visible as basophilic fibrillary structures in H & E stains and in silver
stains
• Seen in cortical neurons of hippocampus, amygdala, basal orebrain, raphe
neuclei
• Paired helical filaments are also found in the dystrophic neurites that form
the outer portions of neuritic plaques and in axons coursing through the
affected gray matter as neuropil threads.
• Tangles are not specific to AD, being found in other diseases as well.
• Pathogenesis
• Alzheimer’s Disease is one of the most common neurodegenerative diseases
worldwide.
• In the normal state,
• In the disease state
Aβ40/42 aggregation results in:
• Alzheimer’s Disease is also characterized by the presence of neurofibrillary
tangles.
• These tangles are the result of hyperphosphorylation of the microtubule
associated protein Tau.
• Hyperphosphorylation of Tau results in the dissociation of Tau from the
microtubule, leading to microtubule destabilization and oligomerization of the
Tau protein within the cell.
• Neurofibrillary tangles form as a result of Tau oligomerization and lead to
apoptosis of the neuron.