CSF neurofilaments in frontotemporal dementia compared with early onset Alzheimer's disease and controls.
BACKGROUND
Frontotemporal dementia (FTD) is pathologically heterogeneous, sometimes revealing intraneuronal inclusions of neurofilaments. We therefore measured CSF neurofilament profiles in patients with FTD, patients with early onset Alzheimer's disease (EAD) and healthy control subjects to explore the discriminative potential of CSF neurofilaments compared with the existing CSF biomarkers amyloid-beta(1-42), tau and tau phosphorylated at threonine-181.


METHODS
CSF levels of light chain, heavy chain and hyperphosphorylated heavy chain neurofilaments (NfL, t-NfH and P-NfH) were compared between 17 subjects with FTD, 20 with EAD and 25 cognitively healthy controls.


RESULTS
A subgroup of FTD patients had remarkably high CSF levels of both NfL and NfH. The degree of NfH phosphorylation was increased in FTD compared to both other groups. The levels of CSF NfL were significantly higher in EAD compared to controls.


CONCLUSIONS
Differences in CSF biomarker profiles might reflect differential involvement of neurofilaments and tau in FTD and EAD. The subgroup of FTD patients with high CSF neurofilament levels may have a different neuropathological substrate and future studies addressing this specific issue are needed.
Pijnenburg
Yolande A L
YA
Department of Neurology, Alzheimer Center, VU University Medical Center, Amsterdam, The Netherlands, and Chelsea and Westminster, Brompton and Charing Cross Hospitals, London, UK. y.pijnenburg@vumc.nl
Janssen
John C
JC
Schoonenboom
Niki S M
NS
Petzold
Axel
A
Mulder
Cees
C
Stigbrand
Torgny
T
Norgren
Niklas
N
Heijst
Hans
H
Hack
C Erik
CE
Scheltens
Philip
P
Teunissen
Charlotte E
CE
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid / Q000378:metabolism; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D003704:Dementia / Q000134:cerebrospinal fluid* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D008875:Middle Aged; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism; D010446:Peptide Fragments / Q000134:cerebrospinal fluid / Q000378:metabolism; D010766:Phosphorylation; D012016:Reference Values; D016875:tau Proteins / Q000134:cerebrospinal fluid* / Q000378:metabolism
D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016900:Neurofilament Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C044882:neurofilament protein L; D016875:tau Proteins