Table 3

Markers of synaptic and neurotransmitter function

Fluid biomarkers	Biological function	Unspecified FTD	PSP	GRN		C9orf72		MAPT		Ref.
Fluid biomarkers	Biological function	Unspecified FTD	PSP	P	S	P	S	P	S	Ref.
SNAP-25	Vesicle fusion and release of neurotransmitters	–								65
Synaptotagmin	Ca²⁺ sensor triggering vesicle fusion on calcium influx	–								65 66
Synaptotagmin	Ca²⁺ sensor triggering vesicle fusion on calcium influx	↓								65 66
Synaptophysin	Synaptic vesicle protein that regulates SNARE assembly and vesicle fusion	↓								66
GAP-43	Ca²⁺-dependent vesicle fusion	–								66
Synapsin 1	Vesicle trafficking	↑								66
Neurogranin	Long-term potentiation and synaptic plasticity and regulates intracellular Ca²⁺ concentration	–								65 66
Neurogranin		↓								65 66
Synaptopodin	Regulates intracellular Ca²⁺ concentration	↓								66
Reelin	Regulation of filopodia formation, dendrite growth and spine formation, and synaptogenesis, modulation of synaptic plasticity and neurotransmitter release	↑								68
NPTXR	Organisation of excitatory and inhibitory synapses	↓		–	↓	–	↓	–	–	69
NPTX2	Modulation of strength of excitatory synapses			–	↓	–	↓	–	–	69
DA	Neurotransmitter	↑								71
DOPAC	DA metabolite	↓								71

Blue, in cerebrospinal fluid; green, in blood and cerebrospinal fluid; red, in blood; yellow, in neuron-derived exosomes from plasma.
– indicates (unchanged levels); ↑ indicates increased levels; ↓ indicates decreased levels; all compared with controls.
C9orf72, chromosome 9 open reading frame 72; DA, dopamine; DOPAC, 3,4-dihydroxyphenylacetic acid; FTD, frontotemporal dementia; GAP-43, growth associated protein, 43 kDa; GRN, progranulin; MAPT, microtubule-associated protein tau; NPTX2, neuronal pentraxin-2; NPTXR, neuronal pentraxin receptor; P, presymptomatic; PSP, progressive supranuclear palsy; Ref, reference; S, symptomatic; SNAP-25, synaptosomal-associated protein, 25 kDa; SNARE, soluble NSF attachment protein receptor.