Table 2 Pooled associations between metabolite levels and disease status/severity of AD pathology.

From: Abnormal brain cholesterol homeostasis in Alzheimer’s disease—a targeted metabolomic and transcriptomic study

 

Disease group

CERAD

Braak

 

ITG

MFG

ITG

MFG

ITG

MFG

Metabolite name

β

P value

β

P value

β

P value

β

P value

β

P value

β

P value

De novo cholesterol biosynthesis

Cholesterol

.

.

−0.062

0.170

.

.

−0.037

0.292

.

.

0.007

0.806

Lanosterol

.

.

−0.278

<0.001

.

.

−0.139

0.012

−0.090

0.050

−0.180

<0.001

24,25-dihydrolanosterol

.

.

.

.

.

.

.

.

−0.032

0.333

.

.

7-dehydrocholesterol

.

.

.

.

.

.

.

.

0.160

0.147

.

.

Desmosterol

Cholesterol catabolism (enzymatic)

27-hydroxycholesterol

0.210

0.170

.

.

0.066

0.555

.

.

0.051

0.641

−0.120

0.223

4β-hydroxycholesterol

0.119

0.234

.

.

0.030

0.688

.

.

.

.

.

.

24S-hydroxycholesterol

−0.113

0.011

.

.

−0.074

0.008

.

.

−0.094

<0.001

−0.087

0.042

7α-hydroxycholesterol

0.154

0.068

.

.

0.135

0.023

.

.

−0.002

0.977

−0.109

0.066

Cholesterol catabolism (non-enzymatic)

5α,6α-epoxycholesterol

0.199

0.040

0.115

0.139

0.118

0.116

0.038

0.508

.

.

.

.

5α,6β-dihydroxycholestanol

0.213

0.017

−0.155

0.088

0.105

0.096

−0.111

0.101

.

.

−0.106

0.062

5β,6β-epoxycholesterol

0.196

0.013

0.071

0.327

0.112

0.069

.

.

0.085

0.152

.

.

7-ketocholesterol

0.304

0.001

.

.

0.179

0.008

.

.

0.102

0.155

−0.035

0.537

7β-hydroxycholesterol

0.237

0.005

.

.

0.157

0.010

.

.

0.050

0.448

−0.089

0.284

  1. ITG Inferior Temporal Gyrus, MFG Middle Frontal Gyrus; P < 0.05 in bold.
  2. Negative coefficients indicate that lower metabolite concentration is significantly associated with AD, higher neuritic plaque burden (CERAD score), or higher neurofibrillary tangle pathology (Braak score). Positive coefficients indicate that higher metabolite concentration is significantly associated with AD, higher neuritic plaque burden (CERAD score), or higher neurofibrillary tangle pathology (Braak score). Blank cells indicate that results were not pooled; these are included in cohort-specific secondary analyses in Supplementary Table 1. Significant associations (P < 0.05) are indicated in bold. Baltimore Longitudinal Study on Aging (BLSA) sample size: AD (n = 15), CN (n = 8); Religious Orders Study (ROS) sample size: AD (n = 31), CN (n = 22); note: samples pooled in analyses.
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