Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults.
OBJECTIVE
The current study examined the association between pulse pressure (PP) and CSF-based biomarkers for Alzheimer disease, including β-amyloid 1-42 (Aβ1-42) and phosphorylated tau (P-tau) protein, in cognitively normal older adults.


METHODS
One hundred seventy-seven cognitively normal, stroke-free older adult participants (aged 55-100 years) underwent blood pressure assessment for determination of PP (systolic - diastolic blood pressure) and lumbar puncture for measurement of CSF Aβ1-42 and P-tau. Pearson correlations and multiple linear regression, controlling for age, sex, APOE genotype, and body mass index, evaluated the relationship between PP and Alzheimer disease biomarkers.


RESULTS
PP elevation was associated with increased P-tau (r = 0.23, p = 0.002), reduced Aβ1-42 (r = -0.19, p = 0.01), and increased P-tau to Aβ1-42 ratio (r = 0.27, p < 0.001). After controlling for covariates, PP remained associated with P-tau (β = 0.18, p = 0.0196) and P-tau to Aβ1-42 ratio (β = 0.0016, p < 0.001) but was no longer associated with Aβ1-42 (β = -0.1, p = 0.35). Post hoc multivariate analyses indicated that increased PP was associated with all biomarkers in younger participants (aged 55-70 years) (Aβ1-42: p = 0.050; P-tau: p = 0.003; P-tau to Aβ ratio: p = 0.0007) but not older participants (aged 70-100 years).


CONCLUSIONS
PP elevation is associated with increased CSF P-tau and decreased Aβ1-42 in cognitively normal older adults, suggesting that pulsatile hemodynamics may be related to amyloidosis and tau-related neurodegeneration. The relationship between PP and CSF biomarkers is age-dependent and observed only in participants in the fifth and sixth decades of life.
From the Veterans Affairs San Diego Healthcare System (D.A.N., M.W.B., L.D.-W.), San Diego; Departments of Neurosciences (S.D.E., D.P.S., D.R.G.) and Psychiatry (M.W.B., L.D.-W.), University of California, San Diego, La Jolla, CA; VA Puget Sound Health Care System (E.R.P.), Mental Illness Research, Education, and Clinical Center, Seattle; Departments of Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle, WA; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; and Portland VA Medical Center (J.F.Q.), Portland, OR.
Daniel A
DA
Nation
Steven D
SD
Edland
Mark W
MW
Bondi
David P
DP
Salmon
Lisa
L
Delano-Wood
Elaine R
ER
Peskind
Joseph F
JF
Quinn
Douglas R
DR
Galasko
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D001794:Blood Pressure / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins