Table 1.
Changes in PACAP levels in human pathological conditions.
| Condition or disease | Patient number | Sample, method | Level ranges | Change of PACAP | Reference |
|---|---|---|---|---|---|
| Neurological and psychiatric diseases | |||||
| Alzheimer’s disease | 9 (vs. 7 controls) | CSF, ELISA | 1.8 vs. 2.1 ng/mL | ↓ (vs. controls), | (26) |
| correlated with DRS–R | |||||
| Alzheimer’s–related cognition decline spectrum | 16 AD (vs. 9 MCI–AD vs. 10 CN) | CSF, ELISA | 1.61 vs. 1.80 vs. 1.61 ng/mL | ↓ (vs. MCI–AD), | (28) |
| ↓ (vs. CN), | |||||
| correlated with DRS–R | |||||
| Parkinson’s disease with dementia | 8 (vs. 7 controls) | CSF, ELISA | 2.1 ng/mL in both | no change | (26) |
| Parkinson’s disease | 72 (vs. 71 controls) | serum, ELISA | 76.02 ± 43.78 vs. 154.96 ± 76.54 pg/mL | ↓ (vs. controls), | (33) |
| negative correlation with attention/memory | |||||
| Parkinson’s disease | 106 (vs. 37 controls) | plasma, ELISA | normalized data only | ↓ (vs. controls), | (34) |
| ↑ in patients with DBS therapy vs. without DBS therapy, | |||||
| correlation with PD subtypes and clinical stages | |||||
| multiple sclerosis | 145 (vs. 73 controls) | serum, ELISA | 57,179.11 vs. 61,419.05 fg/mL, | no change (vs. controls), | (37) |
| female patients 62,466.400 vs. male patients 48,516.214 fg/mL | ↑ in female vs. male patients | ||||
| multiple sclerosis | 20 (vs. 27 controls) | plasma and CSF, ELISA | plasma: 4.20 ± 3.03 vs. 4.23 ± 2.64 pg/mL | no change in plasma | (38) |
| CSF: 4.15 ± 1.23 vs. 6.72 ± 3.12 pg/mL | ↓ (vs. controls) in CSF | ||||
| migraine | 38 (vs. 20 controls) | plasma, ELISA | interictal: 1929 ± 706 and ictal: 1638 ± 738 vs. 830 ± 275 pg/mL | ↑ (vs. controls), | (43) |
| no change ictal vs. interictal, | |||||
| negative correlation with attack frequency per month | |||||
| migraine | 87 (vs. 40 controls) | plasma, RIA | interictal: 24.60 ± 3.59 and ictal: 27.39 ± 4.67 vs. 26.54 ± 4.43 fmol/mL | ↓ interictal vs. controls | (44) |
| ↓ interictal and ↑ ictal | |||||
| migraine with sumatriptan treatment | 15 | plasma, RIA | interictal: 21 ± 3 vs. ictal: 36 ± 3 vs. 1 h after treatment: 26 ± 3 pmol/L | ↓ interictal and ↑ ictal | (45) |
| ↓ after treatment | |||||
| migraine | 26 | plasma, RIA | normalized data only | correlation with alterations of the white matter microstructure detected by diffusion MRI | (46) |
| chronic vs. episodic migraine | 86 vs. 35 (vs. 32 controls) | serum, ELISA | 109.8 ± 43.8 vs. 98.8 ± 34.3 vs. 108.7 ± 43.0 pg/mL | no change (vs. controls) | (47) |
| chronic vs. episodic migraine | 101 vs. 98 (vs. 97 controls) | serum, ELISA | 204.931 (101.08–597.64) vs. 94.992 (65.77–128.48) vs. 103.142 (59.42–123.97) pg/mL [median and (IQ)] | ↑ in chronic migraine (vs. episodic and controls) | (48) |
| chronic vs. episodic migraine | 36 vs. 23 (vs. 30 controls) | serum, ELISA | 2.72 (1.06) vs. 2.73 (0.46) vs. 2.57 (0.64) ng/mL [median and (IQR)] | ↑ in episodic migraine vs. controls, | (49) |
| no change in chronic migraine vs. controls | |||||
| effect of aerobic training on migraineurs | 15 + 15 (vs. 15 controls) | plasma, ELISA | normalized data only | no change (vs. controls) | (50) |
| episodic cluster headache | 9 (vs. 9 controls) | plasma, RIA | inter–bout: 24.4 (2.68) vs. 30.5 (8.84) fmol/mL, ictal: 28.8 (3.40) vs. 30.5 (8.84) fmol/mL [median and (IQR)] | ↓ in inter–bout period, | (51) |
| ↑ in attack period | |||||
| episodic vs. chronic cluster headache | 18 vs. 13 | plasma, RIA | 4.0 ± 0.8 vs. 3.3 ± 0.7 pmol/L | ↑ in episodic cluster headache patients in active phase | (52) |
| headache associated with vs. without pituitary adenoma | 33 vs. 30 | plasma, ELISA | 23.32 ± 6.51 vs. 20.51 ± 4.73 pmol/L | ↑ in headache associated with pituitary adenoma, | (53) |
| PACAP concentration remained high in patients who had little improvement in headache | |||||
| generalized anxiety disorder | 88 (vs. 110 controls) | plasma, RIA | normalized data only | ↓ in females only | (59) |
| effect of acute stress | 10 (vs. 20 controls) | blood, ELISA | normalized data only | ↑ both groups | (60) |
| post–traumatic stress disorder | 64 | plasma, RIA | low: < 20 pM, | ↑ in females only | (61) |
| high: > 20 pM | correlated with symptoms in females only | ||||
| Cardiovascular and cerebrovascular diseases | |||||
| heart failure in primary dilated vs. ischemic cardiomyopathy | 9 vs. 33 | plasma, RIA | normalized data only | ↓ in HF with ischemic background, | (71) |
| negative correlation with NT–proBNP in ischemic group, | |||||
| positive correlation with systolic left ventricular function in ischemic group | |||||
| acute vs. chronic heart failure | 13 vs. 33 (vs. 13 controls) | plasma, ELISA | normalized data only | ↑ in acute HF, | (72) |
| ↓ in chronic HF, | |||||
| negative correlation with NT–proBNP in case of chronic HF, | |||||
| positive correlation with CRP in merged group, | |||||
| positive correlation with low cytokine levels in case of chronic HF | |||||
| ST–segment elevation myocardial infarction | 16 (vs. 12 controls) | plasma, ELISA | normalized data only | ↑ in STEMI before intervention, | (73) |
| ↓ in STEMI after intervention, | |||||
| negative correlation with cardiac troponin in patient group | |||||
| non–traumatic basal ganglia hemorrhage | 150 (vs. 150 controls) | plasma, ELISA | 268.0 ± 112.6 vs. 72.0 ± 24.2 pg/mL | ↑ (vs. controls), | (98) |
| positive correlation with NIHSS scores and hematoma volume, | |||||
| independent predictor for mortality | |||||
| non–traumatic aneurysmal subarachnoid hemorrhage | 118 (vs. 118 controls) | plasma, ELISA | 296.6 ± 119.7 vs. 77.1 ± 17.9 pg/mL | ↑ (vs. controls), | (99) |
| positive correlation with WFNS and Fisher score, | |||||
| independent predictor for mortality | |||||
| Diseases of the gastrointestinal tract and the kidney | |||||
| nephrotic syndrome | 28 (vs.10 controls) | plasma and urine, WB | normalized data only | ↓ in plasma (vs. controls), | (105) |
| ↑ in urine (vs. controls), | |||||
| ↑ after nephrectomy | |||||
| chronic hepatitis B with lamivudine therapy | 25 (vs. 25 controls) | plasma, RIA | before treatment 22.62 ± 8.27, after treatment: 49.6 ± 16.45 vs. 65.18 ± 12.61 pg/mL | ↓ (vs. controls), | (106) |
| ↑ after treatment | |||||
| liver cirrhosis | 113 (vs. 110 controls) | plasma, ELISA | 306.1 ± 55.1 vs. 385.5 ± 48.9 mg/dL | ↓ (vs. controls), | (107) |
| negative correlation with clinical stages | |||||
| Diseases of the musculoskeletal system | |||||
| primary knee osteoarthrosis | 101 (vs. 62 controls) | serum and SF, ELISA | serum: 93.2 ± 12.5 pg/mL vs. 94.9 ± 15.5 pg/mL, | no change (vs. controls) in serum, | (114) |
| ↓ in SF, | |||||
| SF: 239.5 ± 36.4 vs. 305.1 ± 12.5 pg/mL | ↑ in SF after HA injection, | ||||
| negative correlation with radiological stages and clinical severity (SF) | |||||
| post–traumatic knee osteoarthrosis | 72 (vs. 60 controls) | serum and SF, ELISA | serum: 86.0 ± 15.3 pg/mL vs. 82.8 ± 19.7 pg/mL, | no change (vs. controls) in serum, | (115) |
| ↓ in SF, | |||||
| SF: 202.0 ± 48.3 vs. 326.0 ± 66.7 pg/mL | negative correlation with radiological stages and clinical severity | ||||
| non–traumatic osteonecrosis of femoral head | 102 (vs. 95 controls) | serum, ELISA | 212.8 ± 24.4 vs. 303.7 ± 19.7 pg/mL | ↓ (vs. controls), | (116) |
| negative correlation with radiological stages and clinical severity | |||||
| postmenopausal osteoporosis | 123 (vs. 120 controls) | serum, ELISA | 55.7 ± 21.3 vs. 91.5 ± 19.5 pg/mL | ↓ (vs. controls), | (117) |
| negative correlation with radiological stages, | |||||
| positive correlation with bone mineral density, negative correlation with clinical severity | |||||
| Critical illness | |||||
| traumatic brain injury | 38 (vs. 14 controls) | plasma and CSF, RIA | plasma: 37.458 ± 12.463 vs. 14.514 ± 3.080 fmol/mL | ↑ in plasma and CSF (vs. controls), | (122) |
| CSF: 28.978 ± 10.116 vs. 16.090 ± 1.018 fmol/mL | correlation with mortality | ||||
| polytrauma | 13 | plasma, ELISA | normalized data only | ↑ days 1–4 (tendency only), | (123) |
| ↓ day 5 (tendency only), | |||||
| positive correlation with CRP on day 4 and 5. | |||||
| coronavirus disease 2019 | 24 | plasma, ELISA | no data | no change | (124) |
PACAP, pituitary adenylate cyclase activating polypeptide; ↑, increase; ↓, decrease; CSF, cerebrospinal fluid; ELISA, enzyme–linked immunosorbent assay; DRS–R, Mattis Dementia Rating Scale–Revised; AD, Alzheimer’s disease; MCI–AD, mild cognitive impairment in Alzheimer’s disease; CN, normal cognitive; DBS, deep brain stimulation; PD, Parkinson’s disease; RIA, radioimmunoassay; MRI, magnetic resonance imaging; IQR, interquartile range; HF, heart failure; NT–proBNP, N–terminal prohormone of brain natriuretic peptide; CRP, C–reactive protein; STEMI, ST–segment elevation myocardial infarction; NIHSS, National Institutes of Health Stroke Scale; WFNS, World Federation of Neurosurgical Societies; WB, Western blot; SF, synovial fluid; HA, hyaluronic acid.