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Differential levels...
Differential levels of apolipoprotein E and butyrylcholinesterase show strong association with pathological signs of Alzheimer's disease in the brain in vivo
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- Darreh-Shori, Taher (author)
- Karolinska Institutet
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- Forsberg, Anton (author)
- Karolinska Institutet
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Modiri, Negar (author)
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- Andreasen, Niels (author)
- Karolinska Institutet
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- Blennow, Kaj, 1958 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
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Kamil, Chelenk (author)
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Ahmed, Hiba (author)
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- Almkvist, Ove (author)
- Karolinska Institutet,Stockholms universitet,Psykologiska institutionen
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- Långström, Bengt (author)
- Uppsala universitet,Institutionen för biokemi och organisk kemi
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Nordberg, Agneta (author)
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(creator_code:org_t)
- Elsevier, 2011
- 2011
- English.
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In: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 32:12, s. 2320.e15-2320.e32
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Abstract
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- Recently, we reported that 3 of the known risk factors of Alzheimer's disease (AD), i.e., advanced age, apolipoprotein E (ApoE) ε4, and female gender, are associated with differential levels of ApoE proteins and butyrylcholinesterase (BuChE) in the cerebrospinal fluid (CSF) of AD patients. The ApoE ε4 allele and certain BuChE polymorphisms synergistically affect the conversion rate of mild cognitive impairment (MCI) to AD. Here, we investigated interrelationships between ApoE and BuChE levels, and pathological markers of AD in vivo. CSF from patients with probable AD, assessed for cerebral glucose metabolism (CMRglc; n = 50) and Pittsburgh compound B (PIB) retention (β-amyloid [Aβ] load, n = 29) by positron emission tomography (PET), was used for measurement of BuChE, ApoE, Aβ, tau, phosphorylated tau (P-tau) and interleukin-1β (IL-1β) levels. Levels of ApoE and BuChE strongly correlated with CMRglc (fluorodeoxyglucose [FDG]-PET, r = 0.54, p < 0.0001, n = 50), cerebral Aβ load (PIB retention, r = 0.73, p < 0.0001, n = 29), and CSF P-tau (r = 0.73, p < 0.0001, n = 33). High ApoE protein was tied to low CMRglc and high PIB retention and P-tau. BuChE levels had opposite relationships. Other CSF covariates were levels of interleukin-1β and Aβ42peptide. The pattern of the patients' cognitive Z-scores strongly supported these observations. High ApoE protein was also linked to changes in 3 of the biodynamic properties of BuChE. In vitro analysis indicated that high ApoE protein levels were related to an increased pool of dormant BuChE molecules with an abnormally high intrinsic catalytic rate in CSF, which was “turned on” by excess Aβ peptides. The findings suggest that abnormally high levels of ApoE may play a causative role in the pathological events of AD, particularly those involving the early cholinergic deficit in the AD brain, through modulation of cholinesterases activities, hence disturbing the acetylcholine-dependent activity of neurons and nonexcitable cells such as glial cells.
Subject headings
- SAMHÄLLSVETENSKAP -- Psykologi (hsv//swe)
- SOCIAL SCIENCES -- Psychology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Geriatrik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Geriatrics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Psykiatri (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Psychiatry (hsv//eng)
Keyword
- apolipoprotein E
- butyrylcholinesterase
- Alzheimer’s disease
- brain
- Psychology
- Psykologi
- Psychology
- psykologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Darreh-Shori, Ta ...
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Forsberg, Anton
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Modiri, Negar
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Andreasen, Niels
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Blennow, Kaj, 19 ...
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Kamil, Chelenk
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show more...
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Ahmed, Hiba
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Almkvist, Ove
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Långström, Bengt
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Nordberg, Agneta
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show less...
- About the subject
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- SOCIAL SCIENCES
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SOCIAL SCIENCES
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and Psychology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Neurosciences
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Geriatrics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Psychiatry
- Articles in the publication
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Neurobiology of ...
- By the university
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Stockholm University
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University of Gothenburg
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Karolinska Institutet
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Uppsala University