Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.
OBJECTIVE
White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia.


METHODS
Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio.


RESULTS
Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups.


CONCLUSIONS
The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden. michael.jonsson@neuro.gu.se
M
M
Jonsson
H
H
Zetterberg
E
E
van Straaten
K
K
Lind
S
S
Syversen
A
A
Edman
K
K
Blennow
L
L
Rosengren
L
L
Pantoni
D
D
Inzitari
A
A
Wallin
D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000134:cerebrospinal fluid; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000134:cerebrospinal fluid* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid; D010766:Phosphorylation; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D012720:Severity of Illness Index; D013129:Spinal Puncture; D013433:Sulfoglycosphingolipids / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism
D000418:Albumins; D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; C054369:MAPT protein, human; D016900:Neurofilament Proteins; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013433:Sulfoglycosphingolipids; C044882:neurofilament protein L; D016875:tau Proteins