Open AccessCerebrospinal fluid ratios with Aβ 42 predict preclinical brain β‐amyloid accumulation
Author(s) -
Racine Annie M.,
Koscik Rebecca L.,
Nicholas Christopher R.,
Clark Lindsay R.,
Okonkwo Ozioma C.,
Oh Jennifer M.,
Hillmer Ansel T.,
Murali Dhanabalan,
Barnhart Todd E.,
Betthauser Tobey J.,
Gallagher Catherine L.,
Rowley Howard A.,
Dowling N. Maritza,
Asthana Sanjay,
Bendlin Barbara B.,
Blennow Kaj,
Zetterberg Henrik,
Carlsson Cynthia M.,
Christian Bradley T.,
Johnson Sterling C.
Publication year - 2015
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1016/j.dadm.2015.11.006
Subject(s) - cerebrospinal fluid , pittsburgh compound b , cognitive decline , amyloid (mycology) , magnetic resonance imaging , medicine , pathology , neuroscience , psychology , alzheimer's disease , oncology , disease , dementia , radiology
Biomarkers are urgently needed for the critical yet understudied preclinical stage of Alzheimer's disease (AD). Methods Cerebrospinal fluid (CSF) collection, [C‐11]Pittsburgh compound B (PiB) amyloid imaging, and magnetic resonance imaging were acquired in 104 cognitively healthy adults enriched with risk for sporadic AD. Image‐derived cerebral β‐amyloid (Aβ) burden, measured concurrently and longitudinally, was regressed on CSF measures of Aβ, neural injury, and inflammation, as well as ratios with Aβ 42 . Linear mixed‐effects regression was used to model the effect of the CSF measures that predicted longitudinal brain amyloid accumulation on longitudinal cognitive decline, measured by memory test scores. Results At baseline, Aβ 42 /Aβ 40 and all CSF ratios to Aβ 42 were associated with PiB binding in AD‐vulnerable regions. Longitudinally, Aβ 42 /Aβ 40 and ratios of total tau (t‐tau), phosphorylated‐tau (p‐tau), neurofilament light protein, and monocyte chemoattractant protein‐1 to Aβ 42 were associated with increased Aβ deposition over 2 years, predominantly in lateral parietal and temporal cortex. However, these CSF ratios were not significantly associated with cognitive decline, and the effect seems to be largely driven by Aβ 42 in the denominator. Discussion These results corroborate previous findings that t‐tau/Aβ 42 and p‐tau/Aβ 42 are the strongest candidate biomarkers during the preclinical time frame. They support a framework in which neural injury and amyloid deposition are likely occurring simultaneously. It may be that neurodegenerative processes influence progressive amyloid accumulation, even in the preclinical time frame. CSF biomarkers for nonspecific axonal injury and inflammation may provide more information at more advanced stages of the preclinical time course.