AIM-PD-AD Emory study, Anatomy CNS & PNS, Classification of nervous system, Spinal nerve, Cerebral Cortex layers

AIM-PD-AD (Emory University)

Aim	Focus	Sample / readout
Aim 1	Brain Proteomics	Define key human-brain pathways from N=1300 samples
Aim 2	Experimental validation	Genetic manipulation of 10-15 candidates from proteomic / transcriptomics across species, Drosophila
Aim 3	Translating into CSF	Paired brain and CSF biomarkers, Emory University samples (n=150), Integrative proteomics → Neuronal toxicity readout, which modules in the brain network had significant overlap with all proteins (black), proteins increased (red) or decreased (blue) in AD CSF

Preliminary Results [from 제목있는 문서]

1. CSF: 1228 proteins (steroid metabolism, blood coagulation, and hormone activity).
2. 1228 proteins (cell structure and energy metabolism, including glycolysis, oxidoreductase activity, and tubulin regulation. As expected, microtubule-associated protein tau (MAPT) was among the most significantly increased protein.
3. determine overlap between brain and CSF proteome → 70% were also detected (1721 out of 2875), 15 brain modules
4. 8 of the 15 overlapping modules harbored a significant number of CSF proteins increased in AD compared to controls (M12, M1, M2, M18, M5, M44, M33, M38), while 2 modules had significant numbers of CSF proteins decreased in AD (M6, M15)
5. Target 22 most representative peptides (in synapse, metabolism and glial)

[Plan]

1. Integrate proteomics: brain and CSF samples (n=150) → nominate 600 BM candidates detectible
2. Assay development for quantitation 400 proteins
3. (replication) Validation in other cohorts
4. Prioritize 200 proteins
5. Validation for BM performance (correlation with clinical severity, endophenotypes) in ADNI 1&2

(proposed) Expand to proteome plasma immunophenotyped microglia (same patients) Longitudinal? of the (proposed)? (non-targeted) lipidomics and metabolomics

Link the brain-based molecular network & BM

Molecular subtyping X

WHAT about lipidome, metabolome, DNA?

Longitudinal X! (effect size of individual BM-crosssectional & longitudinal)

For BM panel development, so how to use in clinical trial?

Anatomy — CNS & PNS

CENTRAL NERVOUS SYSTEM (Brain - Spinal Cord)

• Protection: Skull
• Nerves: Cranial (12)

Function	Number
Motor

SPINAL CORD

• Protection: Vertebrae
• Nerves: Spinal (31 Pair)

Location	No. of Pairs	Sense	Motor / Sense
Cervical	8
Thoracic	12
Lumbar
Sacral
Coccyx

PERIPHERAL NERVOUS SYSTEM (PNS) (Extension of Central CNS)

• SOMATIC SYSTEM (Reacts to Outside Stimuli)
• AUTONOMIC SYSTEM (Maintains homeostasis)
  • SYMPATHETIC SYSTEM
    • Origin: Thoracic / Lumbar
    • Response: Involuntary
  • PARASYMPATHETIC SYSTEM
    • Origin: Brain / Sacral
    • Response: Normal

Classification of nervous system

• Somatic nervous system
  • Cranial nerves
  • Spinal nerves (except optic n) — With the exception of the olfactory nerve (I) and optic nerve (II), all the nuclei are present in the brainstem.[3]
• Autonomic nervous system
  • Sympathetic
  • Parasympathetic

Spinal nerve

Js: sciatic n is a part of spinal nerve.

spinal nerves (and their dorsal & ventral roots) are part of the PNS.

This is nothing to do with SCI!

spinal nerve is a mixed nerve, formed from the combination of nerve fibers from its dorsal and ventral roots.

곳에서 별개로 시작 분기

• 둘이 일단 합쳐졌다가
• dorsal root, dorsal ramus
• ventral root, ventral / dorsal ramus

ramus	territory	function
dorsal ramus	posterior portions of the trunk	visceral motor, somatic motor, sensory information to and from the skin and muscles of the back
ventral ramus	anterior parts of the trunk and the upper and lower limbs (hypaxial muscles)	visceral motor, somatic motor, and sensory information to and from the ventrolateral body surface, structures in the body wall, and the limbs

Cerebral Cortex

6 layers

Most of the neurons in the cerebral cortex are arranged vertically and most abundant neurons are the efferent pyramidal cells.

There are between 14 and 16 billion neurons in the cerebral cortex.

Layer	Name	Description
I	Molecular layer (lamina molecularis)	consists only a few nerve cells
II	External granular layer (lamina granularis externa)	relatively thin layer consisting of numerous small, densely packed neurons
III	Pyramidal layer or external pyramidal layer (lamina pyramidalis externa)	composed of medium-sized pyramidal nerve cells
IV	Inner granular layer (lamina granularis interna)	relatively thin layer composed of medium-sized cells / contains small, irregularly shaped nerve cells
V	Ganglionic or inner pyramidal layer (lamina pyramidalis interna)	includes large pyramidal cells
VI	Multiform layer (lamina multiformis)	small polymorphic and fusiform nerve cells

pyramidal layers are more developed in the motor centres and granular layers are more developed in sensory centres of the cerebral cortex.

very large giant pyramidal cells found in the layer V of the regions of the motor cortex are called Betz cells.