. 2021 Oct 27;3(4):fcab261. doi: 10.1093/braincomms/fcab261

Table 2.

Biomarker VGF-derived peptides; production, peptide identification method and biomarker of disease pathology

Human VGF peptide	Human VGF cleavage sites and protease if known	Peptide identification method	Biomarker of disease pathology	References
VGF_23–62 (APPG-40)	A22-A23; A62-R63	SELDI-TOF-MS in CSF	Schizophrenia/psychosis: ↑ in CSF from first-onset drug-naïve patients compared to controls; ↑ in CSF compared to Alzheimer’s disease, MDD, and OCD; ↑ in CSF from patients with psychotic depression compared to schizophrenia	⁸⁵ ^, ⁸⁶
VGF_23–174 (APPG-152)	A22-A23; A174-K175	ELISA in serum	MDD: ↓ in serum compared to controls, rescued with 8 weeks of treatment with antidepressants; associated with ↑ risk for suicide	⁸⁷ ^, ⁸⁸
VGF_26–59 (GRPE-34)	P25-G26; V59-R60	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_26–62 (GRPE-37)	P25-G26; A62-R63	SELDI-TOF-MS, MS/MS in CSF	FTD: ↓ in CSF compared to controls Schizophrenia/psychosis: stable in CSF from first-onset drug-naïve patients compared to controls	⁸⁵ ^, ⁹⁰
VGF_41–52 (EPVA-12)	K40-E41; K52-D53	PRM-MS in CSF	FTD: ↓ in CSF from symptomatic GRN mutation carriers compared to non-carriers and pre-symptomatic carriers	⁹¹
VGF_53–60 (DGSA-8)	K52-D53; R60-G61	DIA-MS in CSF	Parkinson’s disease: ↓ in CSF compared to controls	⁹²
VGF_64–80 (NSEP-17)	R63-N64; R80-A81	LC-MS in CSF; DIA-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, predicts conversion from MCI to Alzheimer’s disease; ↓ in CSF compared to MCI Parkinson’s disease: ↓ in CSF compared to controls	^92–96
VGF_78–340 (DPRA-263)	V77-D78; G340-A341	ELISA in CSF and plasma	ALS: ↓ with muscle weakness in CSF compared to controls; ↓ in CSF and plasma from pre-symptomatic SOD1-G93A mice compared to wild-type mice	⁹⁷
VGF_168–176 (DFSP-9)	R167-D168; R176-Q177	LC-ESI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_195–205 (VNLE-11)	R194-V195; V205-W206	SWATH-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, correlates with cognitive decline and dementia severity	⁹⁸
VGF_208–216 (ASWG-9)	R207-A208; R216-V217	LC-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, predicts conversion from MCI to Alzheimer’s disease	⁹⁵ ^, ⁹⁹
VGF_235–247 (MPDS-13)	R234-M235; F247-G248	SWATH-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, correlates with cognitive decline and dementia severity	⁹⁸
VGF_256–267 (THLG-12)	K255-T256; K267-A268	LC-MS and PRM-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, predicts conversion from MCI to Alzheimer’s disease FTD: ↓ in CSF from symptomatic GRN mutation carriers compared to non-carriers and pre-symptomatic carriers	⁹¹ ^, ⁹⁵ ^, ⁹⁹
VGF_268–278 (AYQG-11)	K267-A268; K278-A279	Tandem Mass Tag-MS and PRM-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls; ↓ in CSF compared to MCI	⁹⁶ ^, ⁹⁹
VGF_268–280 (AYQG-13)	K267-A268; R280-R281	LC-ESI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_281–295 (RPES-15)	R280-R281 (PC1/3 or PC2); R295-L296	SWATH-MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls, correlates with cognitive decline and dementia severity	⁹⁸
VGF_281–306 (NERP-1)	R280-R281 (PC1/3 or PC2); A306-G307	Immunohistochemistry in parietal, frontal and temporal cortex	Alzheimer’s disease: ↓ VGF_298–306 in parietal cortex compared to controls Parkinson’s disease: ↓ VGF_298–306 in parietal cortex compared to controls	²⁷
VGF_296–309 (LLQQ-14)	R295-L296; R309-Q310 (PC1/3 or PC2)	DIA-MS in CSF	Parkinson’s disease: ↓ in CSF compared to controls	⁹²
VGF_350–367 (GLQE-18)	R349-G350; A367-E368	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_350–370 (GLQE-21)	R349-G350; E370-R371	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_351–370 (LQEA-20)	G350-L351; E370-R371	LC-MS/MS and targeted-MS/MS in rat cerebellum	Potential biomarker of ageing	²⁴
VGF_373–397 (GGEE-25)	R372-G373; R397-A398	DIA-MS in CSF	Parkinson’s disease: ↓ in CSF compared to controls	⁹²
VGF_373–402 (GGEE-30)	R372-G373; A402-L403	LC-ESI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_373–415 (GGEE-43)	R372-G373; A415-E416	LC-ESI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_373–417 (GGEE-45)	R372-G373; D417-K418	ELISA in CSF	Lewy body disease: ↓ in CSF compared to Alzheimer’s disease or controls	¹⁰⁰ ^, ¹⁰¹
VGF_398–411 (ARQN-14)	R397-A398; G411-E412	SELDI-TOF-MS in CSF	ALS: ↓ in CSF compared to controls	⁹⁷ ^, ¹⁰²
VGF_419–427 (TPGH)	K418-R419 (PC1/3 or PC2); H427-R428 (PC1/3 or PC2)	Immunohistochemistry in parietal, frontal and temporal cortex	Alzheimer’s disease: ↓ in parietal cortex compared to controls Parkinson’s disease: ↓ in parietal cortex compared to controls	²⁷
VGF_485–495 (NAPP-11)	K484-N485 (PC1/3 or PC2); R495-A496	DIA-MS in CSF	Parkinson’s disease: ↓ in CSF compared to controls	⁹²
VGF_485–503 (NAPP-19)	K484-N485 (PC1/3 or PC2); V503-R504	LC-ESI MS, LC-MALDI MS and ELISA in CSF	DLB: ↓ in CSF compared to Alzheimer’s disease or controls Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹ ^, ¹⁰⁰
VGF_485–507 (NERP-4)	K484-N485 (PC1/3 or PC2); Q507-P508	ELISA in plasma	Parkinson’s disease: ↓ in plasma compared to controls, rescued with >6 years of levodopa treatment; negatively correlates with odour discrimination tests	¹⁰³
VGF_485–615 (NAPP-129)	K484-N485 (PC1/3 or PC2)	Gel chromatography, MS and ELISA in plasma	ALS: ↓ in plasma and cultured fibroblasts compared to controls Parkinson’s disease: ↓ in plasma compared to controls, rescued with >6 years of levodopa treatment; negatively correlates with odour discrimination tests	¹³ ^, ¹⁰¹
VGF_486–495 (APPE-10)	N485-A486; R495-A496	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_486–503 (APPE-18)	N485-A486; V503-R504	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_496–504 (APPE-9)	R495-A496; R504-S505	DIA-MS in CSF	Parkinson’s disease: ↓ in CSF compared to controls	⁹²
VGF_507–522 (QPPP-16)	P506-Q507; D522-W523	LC-ESI MS and LC-MALDI MS in CSF	Alzheimer’s disease: ↓ in CSF compared to controls	⁸⁹
VGF_514–610 (APAR-97)	P513-A514; V610-L611	Antibody suspension bead arrays in CSF	FTD: ↓ in bvFTD CSF compared to pre-symptomatic mutation carriers and non-carriers	¹⁰⁴
VGF_554–574 (TLQP-21)	R553-T554 (PC1/3); R574-H575	Immunohistochemistry in parietal, frontal and temporal cortex; gel chromatography and MS in plasma	Alzheimer’s disease: ↓ VGF_556–565 in parietal cortex compared to controls ALS: ↓ in plasma and cultured fibroblasts compared to controls; ↓ in early- and late-stage disease compared to controls Schizophrenia/psychosis: ↑ in prefrontal cortex, ↓ in nucleus accumbens	¹³ ^, ²⁷ ^, ⁶¹ ^, ¹⁰⁵
VGF_554–615 (TLQP-62)	R553-T554 (PC1/3)	Immunohistochemistry in parietal, frontal and temporal cortex; gel chromatography and MS in plasma	Alzheimer’s disease: ↓ VGF_556–565 in parietal cortex compared to controls ALS: ↓ in plasma and cultured fibroblasts compared to controls; ↓ in early- and late-stage disease compared to controls Schizophrenia/psychosis: ↑ in prefrontal cortex, ↓ in nucleus accumbens	¹³ ^, ²⁷ ^, ⁶¹ ^, ¹⁰⁵
VGF_586–595 (AQEE-10)	R585-A586 (PC1/3 or PC2); R595-R596	SRM-MS in CSF	DLB: ↓ in CSF compared to Alzheimer’s disease or controls	¹⁰¹
VGF_586–615 (AQEE-30)	R585-A586 (PC1/3 or PC2)	Gel chromatography and MS in plasma, ELISA in CSF	ALS: ↓ in plasma and cultured fibroblasts compared to controls; ↓ with muscle weakness in CSF compared to controls; ↓ in CSF and plasma from pre-symptomatic SOD1-G93A mice compared to wild-type mice	¹³
VGF_591–610 (EAEE-20)	A590-E591; V610-L611	ELISA in serum	MDD: ↓ in serum compared to controls BD: ↑ in serum compared to controls	¹⁰⁶
VGF_607–615 (C-terminus)	Y606-I607	Immunohistochemistry in parietal, frontal, and temporal cortex	Alzheimer’s disease: ↓ in parietal cortex compared to controls	²⁷

LC-ESI = liquid chromatography-electrospray ionization; LC-MALDI = liquid chromatography matrix assisted laser desorption ionization-time of flight-mass spectrometry.