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P2‐017: Monocyte chemo‐attractant protein (MCP1) links microglia activation to predementia white matter (WM) tract integrity changes
Author(s) -
Fladby Tormod,
Bjerke Maria,
Bjørnerud Atle,
Blennow Kaj,
Gjerstad Leif,
Kjærvik Veslemøy Krohn,
Wallin Anders,
Zetterberg Henrik,
Aarsland Dag,
Selnes Per
Publication year - 2012
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2012.05.720
Subject(s) - pathogenesis , microglia , medicine , apolipoprotein e , white matter , dementia , inflammation , cerebrospinal fluid , neuroinflammation , immunology , pathology , magnetic resonance imaging , disease , radiology
Background: The regulation of CSF Aß42 is poorly understood. Recent studies show Aß42 levels affected by sleep, stress, diet, depression, ApoE genotype, white matter lesions (WML), and Aß plaques. The purpose of this study was to examine the heterogeneity of Aß42 as related to ApoE genotype when interacting with known AD risk factors in healthy, cognitively normal subjects.Methods: In cross-section, we examined the Aß42, T-Tau and P-tau levels as predicted by ApoE4 status in its interaction with depressive symptoms (HAM-D), MRI white-matter hyperintensity volume (WMH V), and memory (Wechsler Logical-Memory). We studied 41 ApoE4+ and 71 ApoE4subjects (mean age 62.0 6 11.9). All participants were non-depressed (HAM-D 10), cognitively normal (CDR 1⁄4 0) and free of MRI brain pathology. Results: ApoE4+ subjects compared to the ApoE4had lower levels of Aß42 (4426 27 vs. 6036 22 ng/L; P <0.01), higher levels of T-Tau (2896 17 vs. 2296 13 ng/L; P<0.01), higher p-Tau (286 1.6 vs. 17 6 21.9ng/L; P <0.01) and higher WMHv (3.77 6 0.41 vs. 2.67 6 0.32 cm 3, P<0.05). Predicting CSF Aß42 levels, controlling for age, we observed three significant 2-way interactions: ApoE genotype X mood, ApoE genotype X memory, ApoE genotype X WMH V (F-values range 1⁄4 4.03-12.35, P<0.05). No interactions were seen for T-tau or P-Tau. Among ApoE4-, mood symptoms, and to a lesser extent worse memory, had a negative correlation with Aß42 (r 1⁄4 .-44, n 1⁄4 71, P <0.01 and r 1⁄4 -.22, n 1⁄4 71, P 1⁄4 0.07). Among ApoE4+ there was a negative correlation between Aß42 and WMH V (r 1⁄4 -0.45, n 1⁄4 26, P<0.05). Conclusions: This is the first study to report the effect of multiple risk factor interactions on CSFAß42 levels in cognitively normal subjects with different ApoE4 alleles. Our results indicate that the relationship between risk factors and CSF Aß42 is dependent on the presence/absence of ApoE4. E4 carriers show reduced CSF Aß42, and lower Aß42 was associated with more MRI-WML; whereas a more typical clinical AD-type phenotype (poor memory, minor depressive symptoms), was associated with decreased CSF Aß42 levels in the ApoE4-non-carriers. These data suggest that Apoe4 carriers and noncarriers may offer divergent trajectories of brain and symptom changes. A better knowledge of the presymptomatic early stages of AD and the interactions with the ApoE4 allele may help us understand the variability of our CSF biomarker measures.