sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study

Brittany Butts; Hanfeng Huang; William T Hu; Patrick Gavin Kehoe; James Scott Miners; Danielle D Verble; Henrik Zetterberg; Liping Zhao; Lynn Marie Trotti; Karima Benameur; Laura M Scorr; Whitney Wharton

doi:10.1002/alz.13457

sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study

Brittany Butts, Hanfeng Huang, William T Hu, Patrick Gavin Kehoe, James Scott Miners, Danielle D Verble, Henrik Zetterberg, Liping Zhao, Lynn Marie Trotti, Karima Benameur, Laura M Scorr, Whitney Wharton^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

4 Citations (Scopus)

Abstract

INTRODUCTION:
There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.

METHODS:
Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.

RESULTS:
CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.

DISCUSSION:
Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.

HIGHLIGHTS:
Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.

Original language	English
Pages (from-to)	1175-1189
Number of pages	15
Journal	Alzheimer's and Dementia
Volume	20
Issue number	2
Early online date	6 Nov 2023
DOIs	https://doi.org/10.1002/alz.13457
Publication status	Published - 1 Feb 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Keywords

Middle Aged
Humans
Alzheimer Disease/pathology
Amyloid beta-Peptides/cerebrospinal fluid
Neuroinflammatory Diseases
Vascular System Injuries
tau Proteins/cerebrospinal fluid
Cognitive Dysfunction/cerebrospinal fluid
Biomarkers/cerebrospinal fluid
Peptide Fragments/cerebrospinal fluid

Access to Document

10.1002/alz.13457

Handle.net

Persistent link

Cite this

@article{72fbb69a90b84fb6b8b6a25254ecdcf2,

title = "sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study",

abstract = "INTRODUCTION:There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.METHODS:Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.RESULTS:CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.DISCUSSION:Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.HIGHLIGHTS:Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.",

keywords = "Middle Aged, Humans, Alzheimer Disease/pathology, Amyloid beta-Peptides/cerebrospinal fluid, Neuroinflammatory Diseases, Vascular System Injuries, tau Proteins/cerebrospinal fluid, Cognitive Dysfunction/cerebrospinal fluid, Biomarkers/cerebrospinal fluid, Peptide Fragments/cerebrospinal fluid",

author = "Brittany Butts and Hanfeng Huang and Hu, {William T} and Kehoe, {Patrick Gavin} and Miners, {James Scott} and Verble, {Danielle D} and Henrik Zetterberg and Liping Zhao and Trotti, {Lynn Marie} and Karima Benameur and Scorr, {Laura M} and Whitney Wharton",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = feb,

day = "1",

doi = "10.1002/alz.13457",

language = "English",

volume = "20",

pages = "1175--1189",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race

T2 - The ASCEND Study

AU - Butts, Brittany

AU - Huang, Hanfeng

AU - Hu, William T

AU - Kehoe, Patrick Gavin

AU - Miners, James Scott

AU - Verble, Danielle D

AU - Zetterberg, Henrik

AU - Zhao, Liping

AU - Trotti, Lynn Marie

AU - Benameur, Karima

AU - Scorr, Laura M

AU - Wharton, Whitney

PY - 2024/2/1

Y1 - 2024/2/1

N2 - INTRODUCTION:There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.METHODS:Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.RESULTS:CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.DISCUSSION:Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.HIGHLIGHTS:Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.

AB - INTRODUCTION:There remains an urgent need to identify preclinical pathophysiological mechanisms of Alzheimer's disease (AD) development in high-risk, racially diverse populations. We explored the relationship between cerebrospinal fluid (CSF) markers of vascular injury and neuroinflammation with AD biomarkers in middle-aged Black/African American (B/AA) and non-Hispanic White (NHW) participants.METHODS:Adults (45-65 years) with a parental history of AD were enrolled (n = 82). CSF and blood biomarkers were collected at baseline and year 2.RESULTS:CSF total tau (t-tau), phosphorylated tau (p-tau), and amyloid beta (Aβ)40 were elevated at year 2 compared to baseline. CSF soluble platelet-derived growth factor receptor β (sPDGFRβ) levels, a marker of pericyte injury, correlated positively with t-tau, p-tau, Aβ40 markers of vascular injury, and cytokines at baseline and year 2. CSF sPDGFRβ and tau were significantly lower in B/AA than NHW.DISCUSSION:Vascular dysfunction and neuroinflammation may precede cognitive decline and disease pathology in the very early preclinical stages of AD, and there are race-related differences in these relationships.HIGHLIGHTS:Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarkers changed over 2 years in high-risk middle-aged adults. Markers of vascular dysfunction were associated with the CSF biomarkers amyloid beta and tau. AD biomarkers were lower in Black compared to non-Hispanic White individuals. Markers of vascular dysfunction were lower among Black individuals.

KW - Middle Aged

KW - Humans

KW - Alzheimer Disease/pathology

KW - Amyloid beta-Peptides/cerebrospinal fluid

KW - Neuroinflammatory Diseases

KW - Vascular System Injuries

KW - tau Proteins/cerebrospinal fluid

KW - Cognitive Dysfunction/cerebrospinal fluid

KW - Biomarkers/cerebrospinal fluid

KW - Peptide Fragments/cerebrospinal fluid

U2 - 10.1002/alz.13457

DO - 10.1002/alz.13457

M3 - Article (Academic Journal)

C2 - 37933404

SN - 1552-5260

VL - 20

SP - 1175

EP - 1189

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 2

ER -

sPDGFRβ and neuroinflammation are associated with AD biomarkers and differ by race: The ASCEND Study

Abstract

Bibliographical note

Keywords

Access to Document

Handle.net

Fingerprint

Cite this