Pathogenesis of Alzheimer's disease: Involvement of the choroid plexus

被引：21

作者：

Carna, Maria ^{[1
]}

Onyango, Isaac. G. ^{[1
]}

Katina, Stanislav ^{[1
,2
]}

Holub, Dusan ^{[3
]}

Novotny, Jan Sebastian ^{[1
]}

Nezvedova, Marketa ^{[4
]}

Jha, Durga ^{[4
]}

Nedelska, Zuzana ^{[1
,5
,6
]}

Lacovich, Valentina ^{[1
]}

Vyvere, Thijs Vande ^{[7
]}

Houbrechts, Ruben ^{[7
]}

Garcia-Mansfield, Krystine ^{[8
]}

Sharma, Ritin ^{[8
]}

David-Dirgo, Victoria ^{[8
]}

Vyhnalek, Martin ^{[1
,5
,6
]}

Texlova, Katerina ^{[1
]}

Chaves, Hernan ^{[9
]}

Bakkar, Nadine ^{[10
]}

Pertierra, Lucia ^{[9
]}

Vinkler, Mojmir ^{[2
]}

Markova, Hana ^{[1
,5
,6
]}

Laczo, Jan ^{[1
,5
,6
]}

Sheardova, Katerina ^{[11
,12
]}

Hortova-Kohoutkova, Marcela ^{[1
]}

Fric, Jan ^{[1
,13
]}

Forte, Giancarlo ^{[1
]}

Kanovsky, Petr ^{[14
,15
]}

Belaskova, Silvie

Damborsky, Jiri ^{[1
,4
]}

Hort, Jakub

Seyfried, Nicholas. T. ^{[16
,17
,18
,19
]}

Bowser, Robert ^{[10
]}

Sevlever, Gustavo ^{[9
]}

Rissman, Robert. A. ^{[20
]}

Smith, Richard. A. ^{[21
]}

Hajduch, Marian ^{[3
]}

Pirrotte, Patrick ^{[8
,22
]}

Spacil, Zdenek ^{[4
]}

Dammer, Eric. B. ^{[16
,17
]}

Limback-Stokin, Clara ^{[23
,24
,27
]}

Stokin, Gorazd. B. ^{[1
,25
,26
]}

机构：

[1] St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic

[2] Masaryk Univ, Inst Math & Stat, Brno, Czech Republic

[3] Palacky Univ Olomouc, Inst Mol & Translat Med, Fac Med & Dent, Olomouc, Czech Republic

[4] Masaryk Univ, Fac Sci, RECETOX Ctr, Brno, Czech Republic

[5] Charles Univ Prague, Fac Med 2, Dept Neurol, Memory Clin, Prague, Czech Republic

[6] Motol Univ Hosp, Prague, Czech Republic

[7] Icometrix, Leuven, Belgium

[8] Translat Genom Res Inst, Collaborat Ctr Translat Mass Spectrometry, Phoenix, AZ USA

[9] FLENI, Buenos Aires, Argentina

[10] Barrow Neurol Inst, Dept Neurobiol, Phoenix, AZ USA

[11] Masaryk Univ, St Annes Univ Hosp, Dept Neurol 1, Brno, MN, Czech Republic

[12] Masaryk Univ, Fac Med, Brno, Oxfordshire, Czech Republic

[13] Inst Hematol & Blood Transfus, Prague, Czech Republic

[14] Palacky Univ Olomouc, Fac Med & Dent, Dept Neurol, Olomouc, Czech Republic

[15] Univ Hosp Olomouc, Res & Sci Dept, Olomouc, Czech Republic

[16] Emory Univ, Sch Med, Ctr Neurodegenerat Dis, Atlanta, GA USA

[17] Emory Univ, Goizueta Alzheimers Dis Res Ctr, Atlanta, GA USA

[18] Emory Univ, Sch Med, Dept Bioachemistry, Atlanta, GA USA

[19] Emory Univ, Dept Neurol, Sch Med, Atlanta, GA USA

[20] Univ Calif San Diego, Dept Neurosci, La Jolla, CA USA

[21] Ctr Neurol Study, La Jolla, CA USA

[22] City Hope Comprehens Canc Ctr, Mass Spectrometry & Prote Core Facil, Duarte, CA USA

[23] Imperial Coll Healthcare NHS Trust, Dept Cellular Pathol, London, England

[24] Imperial Coll London, Fac Med, London, England

[25] Univ Med Ctr, Div Neurol, Ljubljana, Slovenia

[26] Mayo Clin, Translat Aging & Neuroscience Program, Rochester, MN USA

[27] Oxford Univ Hosp NHS Fdn Trust, Neuropathol & Ocular Pathol Dept, Oxford, England

来源：

ALZHEIMERS & DEMENTIA | 2023年 / 19卷 / 08期

关键词：

aging; Alzheimer's disease; cerebrospinal fluid; choroid plexus; pathology; CEREBROSPINAL-FLUID PRODUCTION; CEREBRAL-CORTEX; SOLUBLE TREM2; LEWY BODIES; AGING BRAIN; TAU-PROTEIN; INFLAMMATION; DEMENTIA; BARRIER; PREVALENCE;

D O I：

10.1002/alz.12970

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The choroid plexus (ChP) produces and is bathed in the cerebrospinal fluid (CSF), which in aging and Alzheimer's disease (AD) shows extensive proteomic alterations including evidence of inflammation. Considering inflammation hampers functions of the involved tissues, the CSF abnormalities reported in these conditions are suggestive of ChP injury. Indeed, several studies document ChP damage in aging and AD, which nevertheless remains to be systematically characterized. We here report that the changes elicited in the CSF by AD are consistent with a perturbed aging process and accompanied by aberrant accumulation of inflammatory signals and metabolically active proteins in the ChP. Magnetic resonance imaging (MRI) imaging shows that these molecular aberrancies correspond to significant remodeling of ChP in AD, which correlates with aging and cognitive decline. Collectively, our preliminary post-mortem and in vivo findings reveal a repertoire of ChP pathologies indicative of its dysfunction and involvement in the pathogenesis of AD. HighlightsCerebrospinal fluid changes associated with aging are perturbed in Alzheimer's diseaseParadoxically, in Alzheimer's disease, the choroid plexus exhibits increased cytokine levels without evidence of inflammatory activation or infiltratesIn Alzheimer's disease, increased choroid plexus volumes correlate with age and cognitive performance

引用

页码：3537 / 3554

页数：18

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