Profound degeneration of wake-promoting neurons in Alzheimer's disease
Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear. We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in m...
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| Veröffentlicht in: | Alzheimer's & dementia 2019-10, Vol.15 (10), p.1253-1263 |
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| creator | Oh, Jun Eser, Rana A. Ehrenberg, Alexander J. Morales, Dulce Petersen, Cathrine Kudlacek, Jessica Dunlop, Sara R. Theofilas, Panos Resende, Elisa D.P.F. Cosme, Celica Alho, Eduardo J.L. Spina, Salvatore Walsh, Christine M. Miller, Bruce L. Seeley, William W. Bittencourt, Jackson C. Neylan, Thomas C. Heinsen, Helmut Grinberg, Lea T. |
| description | Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear.
We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls.
The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD.
WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP. |
| doi_str_mv | 10.1016/j.jalz.2019.06.3916 |
| format | Article |
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We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls.
The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD.
WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP.</description><identifier>ISSN: 1552-5260</identifier><identifier>EISSN: 1552-5279</identifier><identifier>DOI: 10.1016/j.jalz.2019.06.3916</identifier><identifier>PMID: 31416793</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Alzheimer's disease ; Autopsy ; Corticobasal degeneration ; Histamine ; Human ; Locus coeruleus ; Orexin ; Progressive supranuclear palsy ; Sleep ; Tauopathies ; Unbiased stereology ; Wake-promoting ; Wakefulness</subject><ispartof>Alzheimer's & dementia, 2019-10, Vol.15 (10), p.1253-1263</ispartof><rights>2019 the Alzheimer's Association</rights><rights>2019 The Alzheimer's Association</rights><rights>Copyright © 2019 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5856-29702dbcbe65512c173c5e4c37bb48a7f2a2f68c568a047d1d027c8a63d71983</citedby><cites>FETCH-LOGICAL-c5856-29702dbcbe65512c173c5e4c37bb48a7f2a2f68c568a047d1d027c8a63d71983</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1016%2Fj.jalz.2019.06.3916$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1016%2Fj.jalz.2019.06.3916$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31416793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oh, Jun</creatorcontrib><creatorcontrib>Eser, Rana A.</creatorcontrib><creatorcontrib>Ehrenberg, Alexander J.</creatorcontrib><creatorcontrib>Morales, Dulce</creatorcontrib><creatorcontrib>Petersen, Cathrine</creatorcontrib><creatorcontrib>Kudlacek, Jessica</creatorcontrib><creatorcontrib>Dunlop, Sara R.</creatorcontrib><creatorcontrib>Theofilas, Panos</creatorcontrib><creatorcontrib>Resende, Elisa D.P.F.</creatorcontrib><creatorcontrib>Cosme, Celica</creatorcontrib><creatorcontrib>Alho, Eduardo J.L.</creatorcontrib><creatorcontrib>Spina, Salvatore</creatorcontrib><creatorcontrib>Walsh, Christine M.</creatorcontrib><creatorcontrib>Miller, Bruce L.</creatorcontrib><creatorcontrib>Seeley, William W.</creatorcontrib><creatorcontrib>Bittencourt, Jackson C.</creatorcontrib><creatorcontrib>Neylan, Thomas C.</creatorcontrib><creatorcontrib>Heinsen, Helmut</creatorcontrib><creatorcontrib>Grinberg, Lea T.</creatorcontrib><title>Profound degeneration of wake-promoting neurons in Alzheimer's disease</title><title>Alzheimer's & dementia</title><addtitle>Alzheimers Dement</addtitle><description>Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear.
We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls.
The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD.
WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP.</description><subject>Alzheimer's disease</subject><subject>Autopsy</subject><subject>Corticobasal degeneration</subject><subject>Histamine</subject><subject>Human</subject><subject>Locus coeruleus</subject><subject>Orexin</subject><subject>Progressive supranuclear palsy</subject><subject>Sleep</subject><subject>Tauopathies</subject><subject>Unbiased stereology</subject><subject>Wake-promoting</subject><subject>Wakefulness</subject><issn>1552-5260</issn><issn>1552-5279</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNqNkU1v3CAQhlHVKt-_oFLlW3OxC9iAfWil1aqbD63UHPaUC8Iw3rC1YQt2ouTX19ZuVsml6oVBzDvPDPMi9JngjGDCv22yjWpfMopJlWGe5RXhH9AJYYymjIrq4-HO8TE6jXGDcYFLwo7QcU4KwkWVn6DFXfCNH5xJDKzBQVC99S7xTfKkfkO6Db7zvXXrxMEQvIuJdcmsfXkA20H4GhNjI6gI5-hTo9oIF_t4hlaLn6v5dbr8dXUzny1TzUrGU1oJTE2ta-CMEaqJyDWDQueirotSiYYq2vBSM14qXAhDDKZCl4rnRpCqzM_Qjx12O9QdGA2uD6qV22A7FZ6lV1a-zzj7INf-UfISk_H3I-ByDwj-zwCxl52NGtpWOfBDlJQKRisseDVK851UBx9jgObQhmA5GSA3cjJATgZIzOVkwFj15e2Eh5rXjY-C-U7wZFt4_h-mnC3vb2_HY3rEfN_m-44C47IfLQQZtQWnwdgAupfG23-O-RfB06zz</recordid><startdate>201910</startdate><enddate>201910</enddate><creator>Oh, Jun</creator><creator>Eser, Rana A.</creator><creator>Ehrenberg, Alexander J.</creator><creator>Morales, Dulce</creator><creator>Petersen, Cathrine</creator><creator>Kudlacek, Jessica</creator><creator>Dunlop, Sara R.</creator><creator>Theofilas, Panos</creator><creator>Resende, Elisa D.P.F.</creator><creator>Cosme, Celica</creator><creator>Alho, Eduardo J.L.</creator><creator>Spina, Salvatore</creator><creator>Walsh, Christine M.</creator><creator>Miller, Bruce L.</creator><creator>Seeley, William W.</creator><creator>Bittencourt, Jackson C.</creator><creator>Neylan, Thomas C.</creator><creator>Heinsen, Helmut</creator><creator>Grinberg, Lea T.</creator><general>Elsevier Inc</general><general>The Alzheimer's Association</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201910</creationdate><title>Profound degeneration of wake-promoting neurons in Alzheimer's disease</title><author>Oh, Jun ; Eser, Rana A. ; Ehrenberg, Alexander J. ; Morales, Dulce ; Petersen, Cathrine ; Kudlacek, Jessica ; Dunlop, Sara R. ; Theofilas, Panos ; Resende, Elisa D.P.F. ; Cosme, Celica ; Alho, Eduardo J.L. ; Spina, Salvatore ; Walsh, Christine M. ; Miller, Bruce L. ; Seeley, William W. ; Bittencourt, Jackson C. ; Neylan, Thomas C. ; Heinsen, Helmut ; Grinberg, Lea T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5856-29702dbcbe65512c173c5e4c37bb48a7f2a2f68c568a047d1d027c8a63d71983</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alzheimer's disease</topic><topic>Autopsy</topic><topic>Corticobasal degeneration</topic><topic>Histamine</topic><topic>Human</topic><topic>Locus coeruleus</topic><topic>Orexin</topic><topic>Progressive supranuclear palsy</topic><topic>Sleep</topic><topic>Tauopathies</topic><topic>Unbiased stereology</topic><topic>Wake-promoting</topic><topic>Wakefulness</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oh, Jun</creatorcontrib><creatorcontrib>Eser, Rana A.</creatorcontrib><creatorcontrib>Ehrenberg, Alexander J.</creatorcontrib><creatorcontrib>Morales, Dulce</creatorcontrib><creatorcontrib>Petersen, Cathrine</creatorcontrib><creatorcontrib>Kudlacek, Jessica</creatorcontrib><creatorcontrib>Dunlop, Sara R.</creatorcontrib><creatorcontrib>Theofilas, Panos</creatorcontrib><creatorcontrib>Resende, Elisa D.P.F.</creatorcontrib><creatorcontrib>Cosme, Celica</creatorcontrib><creatorcontrib>Alho, Eduardo J.L.</creatorcontrib><creatorcontrib>Spina, Salvatore</creatorcontrib><creatorcontrib>Walsh, Christine M.</creatorcontrib><creatorcontrib>Miller, Bruce L.</creatorcontrib><creatorcontrib>Seeley, William W.</creatorcontrib><creatorcontrib>Bittencourt, Jackson C.</creatorcontrib><creatorcontrib>Neylan, Thomas C.</creatorcontrib><creatorcontrib>Heinsen, Helmut</creatorcontrib><creatorcontrib>Grinberg, Lea T.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Alzheimer's & dementia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oh, Jun</au><au>Eser, Rana A.</au><au>Ehrenberg, Alexander J.</au><au>Morales, Dulce</au><au>Petersen, Cathrine</au><au>Kudlacek, Jessica</au><au>Dunlop, Sara R.</au><au>Theofilas, Panos</au><au>Resende, Elisa D.P.F.</au><au>Cosme, Celica</au><au>Alho, Eduardo J.L.</au><au>Spina, Salvatore</au><au>Walsh, Christine M.</au><au>Miller, Bruce L.</au><au>Seeley, William W.</au><au>Bittencourt, Jackson C.</au><au>Neylan, Thomas C.</au><au>Heinsen, Helmut</au><au>Grinberg, Lea T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Profound degeneration of wake-promoting neurons in Alzheimer's disease</atitle><jtitle>Alzheimer's & dementia</jtitle><addtitle>Alzheimers Dement</addtitle><date>2019-10</date><risdate>2019</risdate><volume>15</volume><issue>10</issue><spage>1253</spage><epage>1263</epage><pages>1253-1263</pages><issn>1552-5260</issn><eissn>1552-5279</eissn><abstract>Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear.
We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls.
The three nuclei studied accumulate considerable amounts of tau inclusions and showed a decrease in neurotransmitter-synthetizing neurons in AD, PSP, and corticobasal degeneration. However, substantial neuronal loss was exclusively found in AD.
WPNs are extremely vulnerable to AD but not to 4 repeat tauopathies. Considering that WPNs are involved early in AD, such degeneration should be included in the models explaining sleep-wake disturbances in AD and considered when designing a clinical intervention. Sparing of WPNs in PSP, a condition featuring hyperinsomnia, suggest that interventions to suppress the arousal system may benefit patients with PSP.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>31416793</pmid><doi>10.1016/j.jalz.2019.06.3916</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Alzheimer's & dementia, 2019-10, Vol.15 (10), p.1253-1263 |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Alzheimer's disease Autopsy Corticobasal degeneration Histamine Human Locus coeruleus Orexin Progressive supranuclear palsy Sleep Tauopathies Unbiased stereology Wake-promoting Wakefulness |
| title | Profound degeneration of wake-promoting neurons in Alzheimer's disease |
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