Table 1.

The main neurobiological mechanisms involved in PD physiopathology are summarized. For each of them, related CSF biomarkers are presented, with a focus on their diagnostic and prognostic values.

Pathophysiological mechanisms	CSF biomarkers	Diagnostic value	Prognostic value
			Motor progression	Cognitive decline
α-Syn misfolding	t-α-syn	↓ in PD versus HC	↑/↓ possible association with worsening of motor symptoms	___
	o-α-syn, p-α-syn	↑ in PD versus HC	___	___
	α-syn aggregates	↑ in PD and other synucleinopathies versus HC and non-synucleinopathies	___	___
Amyloidosis	Aβ42	↓ in PDD and ↓↓ in DLB versus PD	___	↓ predicts earlier cognitive decline
Tauopathy	p-tau	___	___	___
Neurodegeneration	t-tau	___	↑ correlation with faster motor progression	___
Axonal damage	NfL	↑ AP in versus PD	___	↑ predicts cognitive decline
Autophagic-lysosomal pathway dysfunctions	GCase	↓ in PD and other synucleinopathies versus HC	↓↓ in the most advanced stages	___
	CTSD, β-hexoxaminidase	↓ in PD versus HC	___	↓ correlates with worse cognitive performances
Neuroinflammation	MCP-1	↑ in PD versus HC	___	___
	YKL-40	↑ in AP versus PD	___	↑ associates to cognitive decline

Abbreviations: Aβ42, amyloid-β peptide 42; APS, atypical parkinsonisms; CTSD, cathepsin D activity; CSF, cerebrospinal fluid; DLB, dementia with Lewy bodies; GCase, glucocerebrosidase activity; HC, healthy control subjects; YKL-40, chitinase-3-like protein 1; MCP-1, monocyte chemoattractant protein-1; o-α-syn, oligomeric α-synuclein; PD, Parkinson’s disease; PDD, Parkinson’s-dementia complex; p-α-syn, phosphorylated α-synuclein; p-tau, phosphorylated tau protein; t-α-syn, total α-synuclein; t-tau, total tau protein.

___, insufficient evidences; ↑, increased levels; ↓, decreased levels.