Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease

Pirttilä, Tuula; Koivisto, Keijo; Mehta, Pankaj; Reinikainen, Kari; Kim, Kwang S.; Kilkku, Olavi; Heinonen, Esa; Soininen, Hilkka; Riekkinen, Paavo; Wı́sniewski, Henryk M.

doi:10.1016/s0304-3940(98)00381-4

Cited by 25 publications

(13 citation statements)

References 18 publications

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“…By contrast, the Australian Imaging, Biomarkers and Lifestyle (AIBL) study showed that ApoE levels were significantly lower in patients with AD and ApoE levels were significantly lower in ε4 homozygous individuals [29]. Other studies have also reported lower ApoE levels in AD [30], [31]. Lower serum ApoE levels were found in carriers of the APOE ε4 allele in another study [32].…”

Section: Discussionmentioning

confidence: 90%

“…A few studies have reported significantly lower ApoE protein in patients with AD [29], [30], [31], [32], [33], while several other studies show increased levels [34], [35], [36]. Similarly the literature on the relationship between APOE ε4 allele and plasma ApoE levels is limited and controversial with some studies showing increased apoE protein levels in APOE ε4 allele carriers [31], [33], [35], while other studies observe the opposite [29], [30]. Furthermore, there is evidence in the literature that the APOE polymorphism may affect the expression level of other apolipoproteins, such as ApoB, as well [16], however fleetingly little work has been done on this topic.…”

Section: Introductionmentioning

confidence: 99%

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Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

et al. 2012

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ObjectivesApolipoproteins have recently been implicated in the etiology of Alzheimer’s disease (AD). In particular, Apolipoprotein J (ApoJ or clusterin) has been proposed as a biomarker of the disease at the pre-dementia stage. We examined a group of apolipoproteins, including ApoA1, ApoA2, ApoB, ApoC3, ApoE, ApoH and ApoJ, in the plasma of a longitudinal community based cohort.Methods664 subjects (257 with Mild Cognitive Impairment [MCI] and 407 with normal cognition), mean age 78 years, from the Sydney Memory and Aging Study (MAS) were followed up over two years. Plasma apolipoprotein levels at baseline (Wave 1) were measured using a multiplex bead fluorescence immunoassay technique.ResultsAt Wave 1, MCI subjects had lower levels of ApoA1, ApoA2 and ApoH, and higher levels of ApoE and ApoJ, and a higher ApoB/ApoA1 ratio. Carriers of the apolipoprotein E ε4 allele had significantly lower levels of plasma ApoE, ApoC3 and ApoH and a significantly higher level of ApoB. Global cognitive scores were correlated positively with ApoH and negatively with ApoJ levels. ApoJ and ApoE levels were correlated negatively with grey matter volume and positively with cerebrospinal fluid (CSF) volume on MRI. Lower ApoA1, ApoA2 and ApoH levels, and higher ApoB/ApoA1 ratio, increased the risk of cognitive decline over two years in cognitively normal individuals. ApoA1 was the most significant predictor of decline. These associations remained after statistically controlling for lipid profile. Higher ApoJ levels predicted white matter atrophy over two years.ConclusionsElderly individuals with MCI have abnormal apolipoprotein levels, which are related to cognitive function and volumetric MRI measures cross-sectionally and are predictive of cognitive impairment in cognitively normal subjects. ApoA1, ApoH and ApoJ are potential plasma biomarkers of cognitive decline in non-demented elderly individuals.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

et al. 2012

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“…To date, the findings on CSF APOE levels in AD remain inconclusive. Some studies found higher concentrations of CSF APOE in patients with AD (Lindh et al 1997; Merched et al 1997), while others found reduced levels of CSF APOE (Blennow et al 1994; Landen et al 1996; Pirttila et al 1998) when compared to the levels in control subjects. Other groups even observed no significant difference in the CSF APOE levels between controls and AD patients (Lefranc et al 1996; Hahne et al 1997).…”

Section: Discussionmentioning

confidence: 99%

APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects

Andrés

Feger

Nath

et al. 2010

J Neuroimmune Pharmacol

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The significance of the cerebrospinal fluid (CSF) Apolipoprotein E (APOE) level and whether it might have differential effects on brain function due to the presence of APOE ε4 allele(s) in HIV-infected patients are unknown. However, APOE ε4 allele has been associated with greater incidence of HIV-associated dementia and accelerated progression of HIV infection. Here, we show further evidence for the role of APOE ε4 in promoting cognitive impairment. We measured the APOE levels in the CSF of HIV-infected individuals. HIV+ subjects showed lower CSF APOE proteins than SN controls (−19%, p=0.03). While SN subjects with or without ε4 allele showed no difference in CSF APOE levels, ε4+ HIV+ subjects had similar levels to the SN subjects but higher levels than ε4− HIV+ subjects (+34%, p=0.01). Furthermore, while HIV+ subjects with ε2 or ε3 allele(s) showed a positive relationship between their CSF APOE levels and cognitive performance on the speed of processing domain (r=+0.35, p=0.05), ε4+ HIV+ subjects, in contrast, exhibited a negative relationship such that those with higher levels of CSF APOE(4) performed worse on the HIV Dementia Scale (r=−0.61, p=0.02), had lower Global Cognitive Scores (r=−0.57, p=0.03), and had poorer performance on tests involving learning (ε4 allele × [APOE] interaction, p=0.01). Our findings also suggest that the relatively higher levels of CSF APOE in ε4+ HIV+ (having primarily APOE4 isoforms) may negatively impact the brain and lead to poorer cognitive outcomes, while those individuals without the ε4 allele (with primarily APOE2 or APOE3 isoforms) may show compensatory responses that lead to better cognitive performance.

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“…144 However, there are opposite results about plasma apoE protein levels in AD. In some reports, a significant lower apoE protein level in AD patients was found, 137,[145][146][147] whereas other studies reported higher levels. [148][149][150] In conclusion, results on the association between apoE-ε4 polymorphism and apoE levels are contradictory.…”

Section: Dementiamentioning

confidence: 99%

“…[148][149][150] In conclusion, results on the association between apoE-ε4 polymorphism and apoE levels are contradictory. 137,145,147,149,150…”

Section: Dementiamentioning

confidence: 99%

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

et al. 2019

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Lipoproteins are the complexes of different lipids and proteins, which are devoted to the transport and clearance of lipids or lipid‐related molecules in the circulation. Lipoproteins have been found to play a crucial role in brain function and may influence myelination process. Among lipoproteins, high‐density lipoproteins (HDLs) and their major protein component, apoA‐I, are directly involved in cholesterol efflux in the brain. It has been suggested that inadequate or dysfunctional brain HDLs may contribute to cerebrovascular dysfunctions, neurodegeneration, or neurovascular instability. HDL deficiency could also promote cognitive decline through impacting on atherosclerotic risk. The focus of this review is to discuss knowledge on HDL dysregulation in neurological disorders. A better understanding on how changes in cellular HDL and apolipoprotein homeostasis affect central nervous system function may provide promising novel avenues for the treatment of specific HDL‐related neurological disorders.

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Longitudinal study of cerebrospinal fluid amyloid proteins and apolipoprotein E in patients with probable Alzheimer's disease

Cited by 25 publications

References 18 publications

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

Plasma Apolipoprotein Levels Are Associated with Cognitive Status and Decline in a Community Cohort of Older Individuals

APOE ε4 allele and CSF APOE on Cognition in HIV-Infected Subjects

Emerging roles for high‐density lipoproteins in neurodegenerative disorders

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