AV133 sample-size tail, Cognition / Cholinergic / Anatomy (basal forebrain BF corticopetal projection / PPN-LDTC / MVN / striatal cholinergic interneurons), Pathway PET enzyme table (ChAT → VAChT → AChE → SDHACU), CUMULATIVE PREVALENCE OF COGNITIVE AND PSYCHIATRIC DISORDERS OR TREATMENT IN PD (Variable / Baseline / Year 1-5)
Cognition / Cholinergic
Anatomy
Four major human brain cholinergic systems are
- the basal forebrain (BF) corticopetal projection system,
- cholinergic efferents of the pedunculopontine-laterodorsal tegmental complex (PPN/LDTC),
- medial vestibular nucleus (MVN) cholinergic neurons projecting to the cerebellum,
- striatal cholinergic interneurons.
Pathway, PET
| synthesis | storage | release | breakdown | Reuptake | |||||
|---|---|---|---|---|---|---|---|---|---|
| Responsible enzyme | Choline acetyltransferase (ChAT): this enzyme is thought to exist primarily in the nerve terminal cytoplasm : (in AD: ↓ChAT) | vesicular acetylcholine transporter (VAChT), | (in AD: ↓AChE) | acetylcholinesterase (AChE), (in AD: ↓AChE) | high-affinity choline transporter (CHT = solute carrier family 5 member 7 = SLC5A7 = ?), sodium-dependent high affinity choline uptake (SDHACU system) | ||||
| Acetylcarnitine → | acetyl coenzyme A (acetylCoA) | Choline 과 합쳐져 | acetylcholine | VAChT is primarily found in the membrane of presynaptic secretory vesicles. It contains 12 transmembrane domains and a synaptic-vesicular-targeting signal located on the intracellular C-terminal tail. The primary function of VAChT is to actively transport cytoplasmic ACh, across an electrochemical gradient, into synaptic vesicles that release ACh upon cell stimulation. The VAChT can affect cholinergic signaling by affecting the relative pools of ACh secreted to activate postsynaptic nicotinic and muscarinic receptors. VAChT is phosphorylated on its serine 480 residue in the C-terminal tail by PKC | To Choline and acetate. (hydrolysis 에 의해) |
약 50% 의 axon terminal back transport / 재활용됨, by a high affinity, Na+-dependent uptake system located predominantly in terminals of cholinergic neurons | |||
| changes in AD | ↓ (particularly in the later stages) | ||||||||
| PD counterpart | AADC | VMAT2 | MAO, COMT | DaT | |||||
| Imaging? | 18F fluoroethoxybenzovesamicol (FEOBV) PET | N-[11C]-methyl-4-piperidyl acetate (MP4A) (ie Acetylcholinesterase PET, analogs of acetylcholine) | |||||||
| [11C]MP4A is specifically hydrolyzed by AChE (99% specificity), and provides a hydrophilic metabolite, N-[11C]methylpiperidinol ([11C]MP4OH), which is trapped in brain because it is too polar to cross the BBB | |||||||||
| (Hilker, 2005 #2795): 17 PDND, 18 PDDLB, 25 controls, PDND: ↓ 5% (NS); PDDLB ↓ 29.7% | |||||||||
| (Klein, 2010 #2796): 8 PDD, 8 DLB, and 9 PDND, in cortex, p can from table 2 | |||||||||
| (Shimada, 2009 #2797): 18 PDND, 21 PDDDLB, 26 HC, in cortex, PDDLB: ↓ 12% PDND, ↓ 23.4%, Fig2; Correlation MP4A, cortical AC vs MMSE: r=0.47, (p=0.005) | |||||||||
|
11C-methylpiperidin-4-yl propionate (11C-PMP) 11C-PMP PET, (Bohnen, 2003 #2798): 11C-PMP and HCN, cortical AChE activity was lowest in PDD (220%), followed by PD (270%) compared with HCs. | |||||||||
| LB | chol col in NBM | 11C MP4A PET | HHSE | |||||
|---|---|---|---|---|---|---|---|---|
| 0 | twin 2012 | 400 | (Hall, 2014 #2803) | 100 | (Shimada 2009) | 29.4 | (Shimada 2009) | |
| 0 | 0.80 0.4% | 40% difference | 200 | 12% (eg 96) | 27.6 | 35% difference | ||
| 1.57 | 200 | 23.4% (eg 77) | 18.0 (↓ 34.7% vs PDND) | |||||
pezil:
- …in rat cortex (Jpn J Pharmacol. 1999 Oct;81(2):216-22. Kosasa T) and hippocampus (Eur J Pharmacol 1999 Sep 10;380(2-3):101-7 Kosasa T) in dose-dependent fashion
- long-term (6 month) 시 ↑ AChE in human CSF : 그래서 치료효과 떨어지나 보다, 가서 효과를 주는 것 아닐까? 마찬가지로 DNPZ+MEM 복합제도 DNPZ 떨어지면 어떤 어떤 가짜 약 ASCOMALVA: , DNPZ 또 어떤 효과 떨어지면 (왜? 효과를 주는 것 아닐까? 마찬가지로 MEM 떨어지면 효과 보내요? (어디 가서 보다)
CUMULATIVE PREVALENCE OF COGNITIVE AND PSYCHIATRIC DISORDERS OR TREATMENT IN PD
| Variable | PD Subjects | |||||
|---|---|---|---|---|---|---|
| Baseline (N = 423) | Year 1 (N = 395) | Year 2 (N = 378) | Year 3 (N = 366) | Year 4 (N = 346) | Year 5 (N = 316) | |
| MOCA <26 | ... | ... | ... | ... | ... | ... |
| GDS-15 | ... | ... | ... | ... | ... | ... |
| N | 423 | 395 | 378 | 366 | 346 | 316 |
| <5 | 311 (73.5%) | 252 (63.8%) | 220 (58.2%) | 198 (54.1%) | 180 (52.0%) | 156 (49.4%) |
| 5 or above | 112 (26.5%) | 143 (36.2%) | 158 (41.8%) | 168 (45.9%) | 166 (48.0%) | 160 (50.6%) |
| STAI State | ... | ... | ... | ... | ... | ... |
Uncertain Spans
| location | transcription | uncertainty |
|---|---|---|
| Hilker 2005 row | ↓ 5% (NS); PDDLB ↓ 29.7% | partly clipped on the right edge; the visible numerical pair is preserved verbatim. |
| Cumulative table / Variable cells | MOCA <26, GDS-15, STAI State raw values | most cell counts beyond the N row are partially clipped on the photo; preserved as ... placeholders where the cell value is not visible. The visible <5 and 5 or above rows under GDS-15 are transcribed verbatim. |
| LB sample-size table | 0.80 / 0.4% cell | reads as written; could be a hand-edited cell with two stacked numbers; preserved verbatim. |