This document discusses dopamine and its relationship to Alzheimer's disease. It provides an overview of dopamine pathways in the brain and its metabolism. Imaging techniques for measuring dopamine like MRI, PET, and tractography are mentioned. Several articles are summarized that show dopamine deficits may be related to cognitive decline in aging and Alzheimer's. Genetic factors like the DAT rs6347 variant and COMT gene are also discussed in the context of dementia severity and psychosis.

1. DOPAMINE &
ALZHEIMER’S
AmirHussein Abdolalizadeh
Interdisciplinary Neuroscience Research Program (INRP), March 2018

2. OVERALL VEIW OVER DOPAMINE

3. BRAIN PATHWAYS
• A major neurotransmitter with modulatory effects
• Involved in many brain systems
• Nigrostriatal pathway: Movement
• Mesolimbic pathway: Reward
• Mesocortical: Executive Function
• Tuberoinfundibular: Endocrine
• Receptors: D1 to D5

4. Metabolism
Degradation:
• MAO (mostly B)
• Monoamine Oxidase
• Oxidative Deamination
• Produces H2O2 & DOPAL
• COMT
• Catechol-O-Methyl Transferase
• Methyl from S-Adenosyl Methionone to
Dopamine
• In glial cells (mostly microglia)
• Produces Homovanilic Acid (HVA)

5. A LITTLE IMAGING

6. GENERAL MRI MEASURES
• Atrophy
• “Brain Shrinkage”
• T1 MRI
• Diffusion MRI
• Physical basis
• Information Provides
• Tractography
• Tissue Properties
• Functional MRI
• BOLD Signal
• Activity dependent

7. PET
• PET basis
• Dopamine Imaging
• Dopamine Transporters
• Dopamine Release

8. ARTICLES

9. • An overview of the amyloid hypothesis
• Ascending dopamine (DA) pathways and synapses with neocortex
• Progressive degeneration of DA nuclei in brainstem  modulation 
• Different sensitivity to A toxicity: DAergics are intermediate
• Normal aging have effects on DAergic system
• Decreased Release
• Reduced D2 expression
• Reduced DA transporter (DAT) expression
• Apathy and Executive function decline: “Unsuccessful aging”
• The earlier the DA deficit occurs  Faster the cognitive decline
• DA agonists improve several domains of cognition in AD patients
• Apathy is the most common DA deficit sign, Extrapyramidals next
• Cluster of AD patients with apathy and CSF tau: limited response to Choline Esterase
Inhibitors,

10. • DAT rs6347: severe dementia and minor allele (C)
• Subjects from ADNI, only non-Hispanics included
• Volume expansion ~ age + sex + diagnosis + APOE + subjects (random factor) +
timepoint (repeated measure)
• More strongly associated with atrophy rather than cognitive measurements, why?

11. • COMT and Psychosis in Schizophrenia: Haplotypes
• AD+P: more severe phenotype of disease
• Val158Met associated with modest increase in Psychosis