Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019;71(1):281-290.
doi: 10.3233/JAD-190077.

Adverse Vascular Risk Relates to Cerebrospinal Fluid Biomarker Evidence of Axonal Injury in the Presence of Alzheimer's Disease Pathology

Katie E Osborn  1 , Jonathan M Alverio  2 , Logan Dumitrescu  1 , Kimberly R Pechman  1 ; Alzheimer’s Disease Neuroimaging Initiative; Katherine A Gifford  1 , Timothy J Hohman  1   3 , Kaj Blennow  4   5 , Henrik Zetterberg  4   5   6   7 , Angela L Jefferson  1
Affiliations

Adverse Vascular Risk Relates to Cerebrospinal Fluid Biomarker Evidence of Axonal Injury in the Presence of Alzheimer's Disease Pathology

Katie E Osborn et al. J Alzheimers Dis. 2019.

Abstract

Background: Vascular risk factors promote cerebral small vessel disease and neuropathological changes, particularly in white matter where large-caliber axons are located. How Alzheimer's disease pathology influences the brain's vulnerability in this regard is not well understood.

Objective: Systemic vascular risk was assessed in relation to cerebrospinal fluid concentrations of neurofilament light, a biomarker of large-caliber axonal injury, evaluating for interactions by clinical and protein markers of Alzheimer's disease.

Methods: Among Alzheimer's Disease Neuroimaging Initiative participants with normal cognition (n = 117), mild cognitive impairment (n = 190), and Alzheimer's disease (n = 95), linear regression related vascular risk (as measured by the modified Framingham Stroke Risk Profile) to neurofilament light, adjusting for age, sex, education, and cognitive diagnosis. Interactions were assessed by cognitive diagnosis, and by cerebrospinal fluid markers of Aβ42, hyperphosphorylated tau, and total tau.

Results: Vascular risk and neurofilament light were not related in the main effect model (p = 0.08). However, interactions emerged for total tau (p = 0.01) and hyperphosphorylated tau (p = 0.002) reflecting vascular risk becoming more associated with cerebrospinal fluid neurofilament light in the context of greater concentrations of tau biomarkers. An interaction also emerged for the Alzheimer's disease biomarker profiles (p = 0.046) where in comparison to the referent 'normal' biomarker group, individuals with abnormal levels of both Aβ42 and total tau showed stronger associations between vascular risk and neurofilament light.

Conclusion: Older adults may be more vulnerable to axonal injury in response to higher vascular risk burdens in the context of concomitant Alzheimer's disease pathology.

Keywords: Alzheimer’s disease; cerebrovascular; neurodegeneration; neurofilament light; vascular risk.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST/DISCLOSURE STATEMENT

The authors have no conflict of interest to report.

Figures

Fig 1.
Fig 1.. FSRP and CSF NFL Stratified by Biomarker Status.
Solid lines reflect unadjusted values of CSF NFL concentration (Y axis, pg/mL) corresponding to modified FSRP score excluding points assigned for age (X axis). Shading reflects 95% confidence interval. Amyloid positive=CSF Aβ42<193 pg/mL; amyloid negative=CSF Aβ42≥193 pg/mL; t-tau positive=t-tau≥93 pg/mL; t-tau negative=t-tau<93 pg/mL; CSF=cerebrospinal fluid, FSRP=Framingham Stroke Risk Profile, NFL=neurofilament light, t-tau=total tau.
Fig 2.
Fig 2.. FSRP and CSF NFL by Alzheimer’s Disease and Suspected Non-AD Pathophysiology (SNAP) Profile.
Solid lines reflect unadjusted values of CSF NFL concentration (Y axis, pg/mL) corresponding to modified FSRP score excluding points assigned for age (X axis). Shading reflects 95% confidence interval; CSF=cerebrospinal fluid, FSRP=Framingham Stroke Risk Profile, NFL=neurofilament light.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Kivipelto M, Helkala EL, Laakso MP, Hanninen T, Hallikainen M, Alhainen K, Soininen H, Tuomilehto J, Nissinen A (2001) Midlife vascular risk factors and Alzheimer’s disease in later life: longitudinal, population based study. BMJ 322, 1447–1451. - PMC - PubMed
    1. Ahtiluoto S, Polvikoski T, Peltonen M, Solomon A, Tuomilehto J, Winblad B, Sulkava R, Kivipelto M (2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75, 1195–1202. - PubMed
    1. Cataldo JK, Prochaska JJ, Glantz SA (2010) Cigarette smoking is a risk factor for Alzheimer’s Disease: an analysis controlling for tobacco industry affiliation. J Alzheimers Dis 19, 465–480. - PMC - PubMed
    1. Aggarwal NT, Bienias JL, Bennett DA, Wilson RS, Morris MC, Schneider JA, Shah RC, Evans DA (2006) The relation of cigarette smoking to incident Alzheimer’s disease in a biracial urban community population. Neuroepidemiology 26, 140–146. - PubMed
    1. Breteler MM, van Swieten JC, Bots ML, Grobbee DE, Claus JJ, van den Hout JH, van Harskamp F, Tanghe HL, de Jong PT, van Gijn J, et al. (1994) Cerebral white matter lesions, vascular risk factors, and cognitive function in a population-based study: the Rotterdam Study. Neurology 44, 1246–1252. - PubMed

Publication types