TABLE 3.
Associations of tight junction proteins with Alzheimer’s disease (AD)-related molecules (apoE, Aβ40, Aβ42, and total tau)
| Association with CLDN5 TX/CD31 TX | Association with OCLN TX/CD31 TX | |||||||
|---|---|---|---|---|---|---|---|---|
| Unadjusted analysis | Adjusting for age at death, sex, CAA score, number of APOE ε4 alleles, Braak stage, and Thai phasellnadjusted analysis | Unadjusted analysis | Adjusting for age at death, sex, CAA score, number of APOE ε4 alleles, Braak stage, and Thai phase | |||||
| Variable | Regression coefficient (95% CI) | P-value | Regression coefficient (95% CI) | P-value | Regression coefficient (95% CI) | P-value | Regression coefficient (95% CI) | P-value |
| Aβ40 TBS | −0.03 (−0.13, 0.06) | .51 | −0.03 (−0.14, 0.07) | .52 | 0.00 (−0.02, 0.03) | .67 | 0.01 (−0.01, 0.03) | .34 |
| Aβ40 TX | −0.04 (−0.14, 0.05) | .36 | −0.06 (−0.16, 0.05) | .32 | −0.02 (−0.04, 0.00) | .11 | −0.02 (−0.04, 0.01) | .20 |
| Aβ40 FA | 0.01 (−0.09, 0.10) | .84 | 0.02 (−0.09, 0.14) | .68 | 0.02 (0.00, 0.04) | .086 | 0.04 (0.01, 0.07) | .002 |
| Aβ42 TBS | −0.23 (−0.32, −0.13) | <.001 | −0.22 (−0.32, −0.13) | <.001 | 0.03 (0.01, 0.05) | .004 | 0.03 (0.01, 0.05) | .0033 |
| Aβ42 TX | −0.12 (−0.21, −0.02) | .017 | −0.10 (−0.20, −0.01) | .031 | 0.04 (0.02, 0.06) | <.001 | 0.05 (0.03, 0.07) | <.001 |
| Aβ42 FA | −0.04 (−0.13, 0.06) | .41 | −0.04 (−0.14, 0.05) | .39 | 0.06 (0.04, 0.08) | <.001 | 0.07 (0.05, 0.09) | <.001 |
| Aβ40/42 TBS | 0.06 (−0.04, 0.15) | .25 | 0.07 (−0.04, 0.17) | .20 | −0.01 (−0.03, 0.01) | .51 | 0.00 (−0.02, 0.02) | .82 |
| Aβ40/42 TX | 0.02 (−0.07, 0.12) | .64 | 0.02 (−0.08, 0.13) | .67 | −0.04 (−0.06, −0.02) | <.001 | −0.05 (−0.07, −0.03) | <.001 |
| Aβ40/42 FA | 0.03 (−0.07, 0.12) | .58 | 0.05 (−0.06, 0.17) | .39 | −0.01 (−0.03, 0.01) | .41 | 0.00 (−0.03, 0.02) | .79 |
| Total tau TBS | −0.38 (−0.47, −0.30) | <.001 | −0.43 (−0.52, −0.34) | <.001 | −0.04 (−0.06, −0.02) | <.001 | −0.05 (−0.07, −0.03) | <.001 |
| Total tau TX | −0.29 (−0.38, −0.20) | <.001 | −0.32 (−0.41, −0.22) | <.001 | 0.02 (0.00, 0.04) | .031 | 0.02 (0.00, 0.04) | .13 |
| Total tau FA | −0.13 (−0.22, −0.03) | .008 | −0.13 (−0.22, −0.03) | .009 | 0.03 (0.01, 0.05) | .005 | 0.03 (0.01, 0.05) | .007 |
| p-tau TBS | −0.07 (−0.17, 0.02) | .11 | −0.08 (−0.17, 0.02) | .12 | 0.02 (−0.00, 0.04) | .077 | 0.02 (0.00, 0.04) | .053 |
| p-tau TX | 0.14 (0.04, 0.23) | .004 | 0.17 (0.07, 0.27) | .001 | 0.06 (0.04, 0.08) | <.001 | 0.08 (0.06, 0.10) | <.001 |
| p-tau FA | −0.17 (−0.27, −0.08) | <.001 | −0.20 (−0.30, −0.09) | <.001 | 0.01 (−0.01, 0.03) | .51 | 0.02 (0.00, 0.05) | .048 |
| apoE TBS | −0.32 (−0.41, −0.23) | <.001 | −0.38 (−0.47, −0.28) | <.001 | −0.06 (−0.08, −0.04) | <.001 | −0.07 (−0.09, −0.05) | <.001 |
| apoE TX | −0.18 (−0.27, −0.09) | <.001 | −0.21 (−0.30, −0.11) | <.001 | −0.06 (−0.08, −0.04) | <.001 | −0.07 (−0.09, −0.05) | <.001 |
| apoE FA | −0.21 (−0.30, −0.11) | <.001 | −0.27 (−0.37, −0.16) | <.001 | −0.01 (−0.03, 0.01) | .18 | −0.01 (−0.03, 0.02) | .61 |
Regression coefficients, 95% CIs, and P-values result from linear regression models, where CLDN5 TX/CD31 TX was considered on the original scale and OCLN TX/CD31 TX was considered on the square root scale. Regression coefficients are interpreted as the change in mean outcome level (CLDN5 TX/CD31 TX or OCLN TX/CD31 TX, on the aforementioned scales) corresponding to each 1-standard-deviation increase in the given variable (on the untransformed, square root transformed, or natural logarithm transformed scale). P-values <.0028 were considered statistically significant after applying a Bonferroni correction for multiple testing separately for each tight junction protein measure; statistically significant associations are shown in bold.
Abbreviation: APOE, apolipoprotein E; CAA, cerebral amyloid angiopathy; CI, confidence interval; CLDN5, claudin-5; FA, formic acid; OCLN, occludin; TBS, Tris-buffered saline; TX, 1% Triton X-100