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Biological Psychology - PSYC133

Overview of Content

This lecture on Biological Psychology outlines essential aspects of Alzheimer's Disease, focusing on core pathological markers, the role of glial cells (specifically microglia), and the implications these have for both the understanding and treatment of the disease. The session aims to provide a comprehensive understanding of the disease's impact on society and the evolving nature of its treatment and management.

Key Terms
  • Alzheimer's Disease: A progressive neurological disorder characterized by gradual cognitive decline and memory loss.
  • Glia: Supportive cells in the nervous system, crucial for maintaining homeostasis and providing support and protection for neurons.
  • Microglia: The primary immune cells of the central nervous system, involved in inflammatory responses and maintaining brain health.

The Role of Glia in Alzheimer’s Disease

This section details the two key components: the nature of Alzheimer’s Disease and the pathophysiological role of microglia.

What is Alzheimer’s Disease?

Alzheimer’s Disease (AD) is a degenerative brain disorder that leads to significant cognitive decline and is the most common form of dementia. It affects approximately 820,000 individuals in the UK. It is categorized primarily into two forms:

  • Early-onset familial AD (less than 65 years old) - 5% of cases.
  • Late-onset sporadic AD (greater than 65 years old) - 95% of cases.
Pathological Markers of Alzheimer’s Disease

  1. Macroscopic Pathology:

    • Features of AD include neuronal atrophy, enlargement of sulci, particularly impacting temporal lobe neurons that are cholinergic and release the neurotransmitter acetylcholine.

  2. Microscopic Pathology:

    • Amyloid plaques: These are toxic structures derived from amyloid precursor protein (APP).
    • Neurofibrillary tangles: Composed of tau protein, indicating dysfunction within neurons.
    • Microglia Activation: These brain immune cells become active and change morphology when responding to amyloid and tau-related damage.
History of Alzheimer’s Disease
  • The first patient diagnosed with Alzheimer’s was Auguste Deter, who presented symptoms such as short-term memory loss, cognitive deficits, auditory hallucinations, and aggressive behavior. Initially termed “pre-senile dementia,” the condition was later named after the psychiatrist Alois Alzheimer following autopsy findings of unique brain pathologies.
Economic Burden
  • Alzheimer’s imposes a significant economic burden, costing approximately £26 billion annually in the UK due to care and lost productivity, with the average cost per patient estimated at £32,250.
  • Projections indicate that the number of dementia cases will double approximately every 20 years, with the greatest increases expected in developing countries.
Clinical Features of Alzheimer’s Disease
  • Early Symptoms:
    • Notable short-term memory loss impacting daily life.
  • Advanced Symptoms:
    • Long-term memory loss, confusion, language impairment, and personality changes along with severe disorientation and visuo-spatial deficits. Anxiety and depression frequently occur, complicating communication with caregivers and elevating healthcare costs.

Microglia and Alzheimer’s Disease

Here we explore the pivotal role of microglia in Alzheimer's pathology, along with their dual function as protectors or aggressors depending on their activation state.

Neuroinflammation and Microglial Function
  • Neuroinflammation is characterized by immune activity within the brain—this is distinct from infection. Microglia constantly monitor brain environments and utilize scavenger receptors to identify and bind to amyloid plaques.
  • Upon activation, microglia transform from a ramified (inactive) state to an amoeboid (active) form, resulting in phagocytosis, the process where they engulf and clear plaques.
The Dual Role of Microglia
  • Microglial activation can lead to both beneficial outcomes (e.g., phagocytosis of debris) and detrimental effects if the activation persists, potentially resulting in neurotoxicity through excessive inflammatory signaling (cytokines).
  • Healthy neurons are known to inhibit microglial activation while damaged neurons trigger it, establishing a feedback loop that can exacerbate neuronal damage when amyloid plaques are present, illustrated as a vicious cycle.
Therapeutic Implications
  • The potential therapeutic modulation of microglial activity suggests that anti-inflammatory drugs, such as ibuprofen, may mitigate the inflammatory processes driving Alzheimer’s pathology. In research, drugs repurposed for inflammatory conditions have shown promise in reducing Alzheimer's risk.
  • Donanemab: This antibody specifically targets β-amyloid, enhancing microglial clearance of plaques, representing a targeted therapeutic strategy aimed at the disease's underlying pathological features.

Summary

Discourse within the scientific community suggests a polarized view regarding microglia's role in Alzheimer's Disease; early activation aids in clearing amyloid, while later activation can become neurotoxic as pathology progresses. Investigating methods to modulate inflammatory processes represents a crucial area for future therapeutic strategies, particularly as current treatments are primarily symptomatic and do not halt or reverse the disease’s course. Further research is needed to understand these complex interactions and devise effective interventions against Alzheimer’s Disease.