|
| Biochemical marker | Gene defect | Relevance to LB disorders | Source of biomarker |
|
| AD lesions | Aβ | APP: K670M/N671L and so forth. PS1: H163R and so forth PS2: N141I and so forth | Deposited in plaques | CSF, plasma |
| Tau | Tauopathy: P301L, N279K, K317M, and so forth | Found in NFT in AD brain, released after neuronal damage | CSF |
|
|
PD/DLB lesions | α-synuclein
(PARK1/4) | A53T, A30P (PD), G209A (DLB), E46K, triplication (PD & DLB) | Mutation → ↑ α-syn aggregation.
LB component, toxic oligomers and protofibrils | CSF, skin cells, platelets |
| β-synuclein | P123H, V70M (DLB) | Inhibit α-syn aggregation: mutant causes degeneration | CSF |
| γ-synuclein | SNP in DLBD | Amyloidogenic: affects neuronal and axonal cytoskeleton | Ventricular CSF |
|
Proteostasis/
oxidative stress | Parkin (PARK 2) | K161N, W453Stop, 202-203delAG, M192L, K211N, and so forth | Ubiquitin E3 ligase, LOF mutation in PD alters mitophagy | ND |
| UCHL-1 (PARK 5) | I93M, S18Y (SNP) | Neuronal deubiquitinating hydrolase; impaired synaptic and cognitive function in AD & PD | ND |
| PINK 1 (PARK 6) | A168P, A217D, E417G, E240K, and so forth (PD) | Mitochondrial serine/threonine kinase; LOF mutation in PD alters mitophagy | ND |
| DJ-1 (PARK7) | M26I, D149A, G78G, R98Q (PD), L166P (PD & DLB) | Redox-dependent chaperone; LOF mutation in PD | CSF, plasma |
| LRRK2 (PARK 8) | G2019S, duplication, triplication (PD) | Gain of function mutant in PD?DLB: interacts with α-syn and tau, and with parkin in apoptotic cell death | ND |
|
| Cytoskeletal | NF | NEFM (PD) | Disrupted NF → abnormal axonal transport; released in cell damage | CSF |
|
| Lysosomal dysfunction | GBA | 84 dupl G, IVS 2 + 1, N370S, L444P (PD) | Gaucher’s disease, abnormal lysosomal function/autophagy in PD | CSF, plasma |
|
| Inflammation | IL-1α, IL-1β, IL-6, TNFα | SNP: IL-1β −511,TNF-α −308 | α-syn-induced microglial activation → ↑ secretion of neuroinflammatory mediators | CSF |
|
