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

来源：

JOURNAL OF ALZHEIMERS DISEASE | 2021年 / 80卷 / 03期

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

页码：1051 / 1065

页数：15

共 39 条

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