Olfactory Impairment Is Related to Tau Pathology and Neuroinflammation in Alzheimer's Disease

被引:40
作者
Klein, Julia [1 ,3 ]
Yan, Xinyu [2 ]
Johnson, Aubrey [1 ]
Tomljanovic, Zeljko [1 ]
Zou, James [1 ]
Polly, Krista [1 ]
Honig, Lawrence S. [1 ]
Brickman, Adam M. [1 ]
Stern, Yaakov [1 ,4 ]
Devanand, D. P. [4 ]
Lee, Seonjoo [2 ,5 ]
Kreisl, William C. [1 ]
机构
[1] Columbia Univ, Taub Inst, Irving Med Ctr, New York, NY USA
[2] Columbia Univ, Mailman Sch Publ Hlth, Irving Med Ctr, New York, NY USA
[3] Weill Cornell Med Coll, New York, NY USA
[4] Columbia Univ, Gertrude H Sergievsky Ctr, Irving Med Ctr, New York, NY 10027 USA
[5] Res Fdn Mental Hyg Inc, New York, NY USA
关键词
Alzheimer's disease; anosmia; microglia; olfaction; tau proteins;
D O I
10.3233/JAD-201149
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Olfactory impairment is evident in Alzheimer's disease (AD); however, its precise relationships with clinical biomarker measures of tau pathology and neuroinflammation are not well understood. Objective: To determine if odor identification performance measured with the University of Pennsylvania Smell Identification Test (UPSIT) is related to in vivo measures of tau pathology and neuroinflammation. Methods: Cognitively normal and cognitively impaired participants were selected from an established research cohort of adults aged 50 and older who underwent neuropsychological testing, brain MRI, and amyloid PET. Fifty-four participants were administered the UPSIT. Forty-one underwent F-18-MK-6240 PET (measuring tau pathology) and fifty-three underwent C-11-PBR28 PET (measuring TSPO, present in activated microglia). Twenty-three participants had lumbar puncture to measure CSF concentrations of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-beta (A beta(42)). Results: Low UPSIT performance was associated with greater F-18-MK-6240 binding in medial temporal cortex, hippocampus, middle/inferior temporal gyri, inferior parietal cortex, and posterior cingulate cortex (p < 0.05). Similar relationships were seen for C-11-PBR28. These relationships were primarily driven by amyloid-positive participants. Lower UPSIT performance was associated with greater CSF concentrations of t-tau and p-tau (p < 0.05). Amyloid status and cognitive status exhibited independent effects on UPSIT performance (p < 0.01). Conclusion: Olfactory identification deficits are related to extent of tau pathology and neuroinflammation, particularly in those with amyloid pathophysiology. The independent association of amyloid-positivity and cognitive impairment with odor identification suggests that low UPSIT performance may be a marker for AD pathophysiology in cognitive normal individuals, although impaired odor identification is associated with both AD and non-AD related neurodegeneration.
引用
收藏
页码:1051 / 1065
页数:15
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