Plasma Glial Fibrillary Acidic Protein Levels Differ Along the Spectra of Amyloid Burden and Clinical Disease Stage.

Abstract

BACKGROUND:

Measuring plasma glial fibrillary acidic protein (GFAP) alongside cortical amyloid-β (Aβ) may shed light on astrocytic changes in aging and Alzheimer's disease (AD).

OBJECTIVE:

To examine associations between plasma GFAP and cortical Aβ deposition in older adults across the typical aging-to-AD dementia spectrum.

METHODS:

We studied two independent samples from UCSF (Cohort 1, N = 50; Cohort 2, N = 37) covering the spectra of clinical severity (CDR Sum of Boxes; CDR-SB) and Aβ-PET burden. Aβ-PET was completed with either florbetapir or Pittsburgh Compound B and standardized uptake value ratios were converted to the Centiloid (CL) scale for analyses. All participants with CDR-SB > 0 were Aβ-PET positive, while clinically normal participants (CDR-SB = 0) were a mix of Aβ-PET positive and negative. Regression analyses evaluated main effect and interaction associations between plasma GFAP, Aβ-PET, and clinical severity.

RESULTS:

In both cohorts, plasma GFAP increased linearly with Aβ-PET CLs in clinically normal older adults. In Cohort 2, which included participants with more severe clinical dysfunction and Aβ-PET burden, the association between Aβ and GFAP became curvilinear (inverted U-shape; quadratic model R2 change = 0.165, p = 0.009), and Aβ-PET interacted with CDR-SB (R2 change = 0.164, p = 0.007): older adults with intermediate functional impairment (CDR-SB = 0.5-4.0) showed a weak (negative) association between Aβ-PET CLs and plasma GFAP, while older adults with dementia (CDR-SB > 4.0) showed a strong, negative association of higher Aβ-PET CLs with lower plasma GFAP.

CONCLUSION:

The relationship between astrocytic integrity and cortical Aβ may be highly dynamic, with linear, positive associations early in disease that diverge in more severe disease stages.

• Authors: Breton M Asken, Fanny M Elahi, Renaud La Joie, Amelia Strom, Adam M Staffaroni, Cutter A Lindbergh, Alexandra C Apple, Michelle You, Sophia Weiner-Light, Nivetha Brathaban, Nicole Fernandes, Anna Karydas, Paul Wang, Julio C Rojas, Adam L Boxer, Bruce L Miller, Gil D Rabinovici, Joel H Kramer, Kaitlin B Casaletto
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 78 Issue 1 Pg. 265-276 ( 2020) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 32986672 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• Amyloid beta-Peptides
• Amyloidogenic Proteins
• Aniline Compounds
• Ethylene Glycols
• Glial Fibrillary Acidic Protein
• Radiopharmaceuticals
• Thiazoles
• tau Proteins
• florbetapir

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (metabolism)
• Amyloid beta-Peptides (metabolism)
• Amyloidogenic Proteins (metabolism)
• Amyloidosis (metabolism)
• Aniline Compounds
• Brain (metabolism)
• Cognitive Dysfunction (metabolism)
• Cohort Studies
• Cross-Sectional Studies
• Ethylene Glycols
• Female
• Glial Fibrillary Acidic Protein (blood)
• Humans
• Male
• Positron-Emission Tomography
• Radiopharmaceuticals (metabolism)
• Thiazoles
• tau Proteins (metabolism)