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Kilander, Lena
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Publications (10 of 62) Show all publications
Skillbäck, T., Lautner, R., Mattsson, N., Schott, J. M., Skoog, I., Nagga, K., . . . Zetterberg, H. (2018). Apolipoprotein E genotypes and longevity across dementia disorders. Alzheimer's & Dementia, 14(7), 895-901
Open this publication in new window or tab >>Apolipoprotein E genotypes and longevity across dementia disorders
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2018 (English)In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 7, p. 895-901Article in journal (Refereed) Published
Abstract [en]

Introduction: The ε4 allele of the apolipoprotein E (APOE) gene is a prominent risk factor for Alzheimer's disease (AD), but its implication in other dementias is less well studied.

Methods: We used a data set on 2858 subjects (1098 AD, 260 vascular dementia [VaD], 145 mixed AD and VaD, 90 other dementia diagnoses, and 1265 controls) to examine the association of APOE polymorphisms with clinical dementia diagnoses, biomarker profiles, and longevity.

Results: The ε4 allele was associated with reduced longevity as ε4 versus ε3 homozygotes lived on average 2.6 years shorter (P = .006). In AD, ε4 carriers lived 1.0 years shorter than noncarriers (P = .028). The ε4 allele was more prevalent in AD, mixed AD and VaD, and VaD patients compared to controls, but not in other dementia disorders.

Discussion: The APOE ε4 allele is influential in AD but might also be of importance in VaD and in mixed AD and VaD, diseases in which concomitant AD pathology is common.

Keywords
Apolipoprotein E, Alzheimer's disease, Dementia with Lewy bodies, Vascular dementia, Frontotemporal dementia, Parkinson's disease dementia, Creutzfeldt-Jakob disease
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-361543 (URN)10.1016/j.jalz.2018.02.003 (DOI)000438783200007 ()29548722 (PubMedID)
Available from: 2018-10-01 Created: 2018-10-01 Last updated: 2018-10-01Bibliographically approved
Velickaite, V., Ferreira, D., Cavallin, L., Lind, L., Ahlström, H., Kilander, L., . . . Larsson, E.-M. (2018). Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data. European Radiology, 28(4), 1739-1747
Open this publication in new window or tab >>Medial temporal lobe atrophy ratings in a large 75-year-old population-based cohort: gender-corrected and education-corrected normative data
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2018 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 28, no 4, p. 1739-1747Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

Keywords
Cognitive test, Dementia, Longitudinal analysis, Medial temporal lobe atrophy (MTA), Population-based, Scheltens’s scale
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-333774 (URN)10.1007/s00330-017-5103-6 (DOI)000426645600044 ()29124383 (PubMedID)
Funder
Stockholm County CouncilThe Karolinska Institutet's Research Foundation
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2018-05-15Bibliographically approved
Nylander, R., Kilander, L., Ahlström, H., Lind, L. & Larsson, E.-M. (2018). Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.. Frontiers in Aging Neuroscience, 10, Article ID 217.
Open this publication in new window or tab >>Small Vessel Disease on Neuroimaging in a 75-Year-Old Cohort (PIVUS): Comparison With Cognitive and Executive Tests.
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2018 (English)In: Frontiers in Aging Neuroscience, ISSN 1663-4365, E-ISSN 1663-4365, Vol. 10, article id 217Article in journal (Refereed) Published
Abstract [en]

Background and Purpose: Signs of small vessel disease (SVD) are commonly seen on magnetic resonance imaging (MRI) of the brain in cognitively healthy elderly individuals, and the clinical relevance of these are often unclear. We have previously described three different MRI manifestations of SVD as well as cerebral perfusion in a longitudinal study of non-demented 75-year-old subjects. The purpose of the present study was to evaluate the relationship of these findings to cognition and executive function at age 75 and changes after 5 years. Methods: In all, 406 subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study were examined with MRI of the brain at age 75 years. Two-hundred and fifty of the subjects were re-examined 5 years later. White matter hyperintensities (WMHs) and lacunar infarcts (LIs) were assessed on both occasions, but microbleeds (MBs) and perfusion only at age 75. Cognitive function was screened by the Mini Mental State Examination (MMSE). Trail Making Test A and B (TMT-A and TMT-B) were performed at baseline and at follow-up at age 80. Results: At baseline, 93% performed >27 points in the MMSE. The TMT-B at age 75 was significantly related to WMH visual scoring after adjustment for sex, education and cerebrovascular disease risk factors (+80 s (95% CI 0.3-161 s), P < 0.05 for grade 2-3 vs. grade 0). Neither MMSE nor TMT-A was significantly related to WMH scoring. There was no relation between any test performance and WMH volume, white matter volume, number of MBs or brain perfusion at age 75. Subjects who had sustained a new LI (n = 26) showed a greater increase of the time to perform TMT-A at the 5-year follow-up (+25 s vs. +4 s in LI-free subjects, P = 0.003). Changes in MMSE or TMT-A and -B test performance between ages 75 and 80 were not related to changes in WMH scoring or volume during the 5 years follow-up, or to brain perfusion at age 75. Conclusion: In this cognitively healthy community-based population, moderate-severe WMHs and incident LIs on brain MRI in individuals aged 75-80 years were associated with a mild impairment of processing speed and executive function.

Keywords
cognitive tests, lacunar infarct, magnetic resonance imaging, perfusion, small vessel disease, white matter hyperintensities
National Category
Geriatrics Gerontology, specialising in Medical and Health Sciences Neurology
Identifiers
urn:nbn:se:uu:diva-356786 (URN)10.3389/fnagi.2018.00217 (DOI)000438723000002 ()30061827 (PubMedID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-09-27Bibliographically approved
Hansen, T., Kilander, L., Ahlström, H. & Lind, L. (2018). Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function. Clinical Physiology and Functional Imaging, 38(3), 373-377
Open this publication in new window or tab >>Total atherosclerotic burden measured by magnetic resonance imaging is related to five-year decline in cognitive function
2018 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 38, no 3, p. 373-377Article in journal (Refereed) Published
Abstract [en]

Objective: The aim of this study was to explore whether total atherosclerotic burden is related to future decline in performance on cognitive tests.

Methods: The total atherosclerotic burden (TAS) was assessed by whole‐body magnetic resonance angiography (WBMRA) in 305 subjects at age 70 in the study Prospective Investigation of Vasculature in Uppsala Seniors (PIVUS). The mini‐mental state examination (MMSE) and trail making tests (TMT) A and B were evaluated at ages 75 and 80 in 190 of those subjects. No subject with a diagnosis of dementia was included in the sample.

Results: MMSE did not change during the 5 years of follow‐up, while TMT A and B increased by 4 and 7 s, respectively. TAS at age 70 was significantly related to the individual change in TMT B (P<0·0001) between age 75 and 80, when adjusted for sex, education level, TMT B at age 75 and Framingham score at age 70. No such relationship was seen for the change in TMT A (P = 0·10). The relationship between TAS and the change in MMSE was of borderline significance (P = 0·025).

Conclusion: A relationship was found between the total atherosclerotic burden and future decline in performance on TMT B, highlighting a role of global atherosclerosis in the cognitive decline seen during ageing.

Keywords
Atherosclerosis, dementia, magnetic resonance angiography, mild cognitive impairment, mini-mental state examination, trail making tests
National Category
Physiology
Identifiers
urn:nbn:se:uu:diva-322144 (URN)10.1111/cpf.12423 (DOI)000430103100005 ()28402078 (PubMedID)
Funder
Swedish Research CouncilAstraZeneca
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2018-06-19Bibliographically approved
Fällmar, D., Lilja, J., Danfors, T., Kilander, L., Iyer, V., Lubberink, M., . . . Sörensen, J. (2018). Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.. American Journal of Nuclear Medicine and Molecular Imaging, 8(4), 239-246
Open this publication in new window or tab >>Z-score maps from low-dose 18F-FDG PET of the brain in neurodegenerative dementia.
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2018 (English)In: American Journal of Nuclear Medicine and Molecular Imaging, ISSN 2160-8407, Vol. 8, no 4, p. 239-246Article in journal (Refereed) Published
Abstract [en]

Neuroimaging is a central part of diagnostic work-up of patients with suspected neurodegenerative disease. FDG-PET can reveal pathological changes earlier and more reliably than morphological imaging. Diagnostic accuracy can be improved by constructing 3D SSP Z-score maps, showing patterns of significant deficits. During FDG-PET, the subject receives a moderate but not insignificant dose of ionizing radiation, and a dose reduction with retained image quality is desirable. With lower dose, repeated examinations can become a useful tool for monitoring disease progress and potential effects of disease-modifying interventions. The aim of this study was to evaluate Z-maps created from low-dose and normal-dose FDG-PET of the brain, with quantitative and qualitative methods. Nine patients with neurodegenerative disorders were prospectively enrolled and nine age-matched controls were recruited through advertising. All subjects (n=18) underwent two FDG-PET scans on separate occasions; a routine and a low-dose scan. The routine dosage of FDG was 3 MBq/kg, and low dosage was 0.75 MBq/kg. 3D-SSP images showing Z-scores of < -1.96 were created from 10-minute summations. The study was comprised of a quantitative part comparing the Z-scores, and a qualitative part where experienced nuclear medicine specialists visually assessed the images. Regarding the quantitative part, Bland-Altman analysis showed a slight constant bias (0.206). Regarding qualitative discrimination between patients and controls, the performance between normal- and low-dose were equal, both showing 72% sensitivity, 83% specificity and 78% accuracy. In this study, visual assessment of 3D-SSP Z-score maps from low-dose FDG-PET provided diagnostic information highly comparable to normal-dose, with minor quantitative discrepancies.

Keywords
FDG, PET, methodology, neurodegeneration, neuroimaging, radiation
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-362198 (URN)000444491000001 ()30245916 (PubMedID)
Available from: 2018-10-02 Created: 2018-10-02 Last updated: 2018-11-15Bibliographically approved
Fällmar, D., Haller, S., Lilja, J., Danfors, T., Kilander, L., Tolboom, N., . . . Larsson, E.-M. (2017). Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.. European Radiology, 27(10), 4237-4246
Open this publication in new window or tab >>Arterial spin labeling-based Z-maps have high specificity and positive predictive value for neurodegenerative dementia compared to FDG-PET.
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2017 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 27, no 10, p. 4237-4246Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: Cerebral perfusion analysis based on arterial spin labeling (ASL) MRI has been proposed as an alternative to FDG-PET in patients with neurodegenerative disease. Z-maps show normal distribution values relating an image to a database of controls. They are routinely used for FDG-PET to demonstrate disease-specific patterns of hypometabolism at the individual level. This study aimed to compare the performance of Z-maps based on ASL to FDG-PET.

METHODS: Data were combined from two separate sites, each cohort consisting of patients with Alzheimer's disease (n = 18 + 7), frontotemporal dementia (n = 12 + 8) and controls (n = 9 + 29). Subjects underwent pseudocontinuous ASL and FDG-PET. Z-maps were created for each subject and modality. Four experienced physicians visually assessed the 166 Z-maps in random order, blinded to modality and diagnosis.

RESULTS: Discrimination of patients versus controls using ASL-based Z-maps yielded high specificity (84%) and positive predictive value (80%), but significantly lower sensitivity compared to FDG-PET-based Z-maps (53% vs. 96%, p < 0.001). Among true-positive cases, correct diagnoses were made in 76% (ASL) and 84% (FDG-PET) (p = 0.168).

CONCLUSION: ASL-based Z-maps can be used for visual assessment of neurodegenerative dementia with high specificity and positive predictive value, but with inferior sensitivity compared to FDG-PET.

KEY POINTS: • ASL-based Z-maps yielded high specificity and positive predictive value in neurodegenerative dementia. • ASL-based Z-maps had significantly lower sensitivity compared to FDG-PET-based Z-maps. • FDG-PET might be reserved for ASL-negative cases where clinical suspicion persists. • Findings were similar at two study sites.

Keywords
18F-FDG, Arterial spin labeling MRI, Dementia, Neurodegenerative, Visual assessment
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-319602 (URN)10.1007/s00330-017-4784-1 (DOI)000408952400027 ()28374078 (PubMedID)
Available from: 2017-04-06 Created: 2017-04-06 Last updated: 2018-01-03Bibliographically approved
Velickaite, V., Giedraitis, V., Ström, K., Alafuzoff, I., Zetterberg, H., Lannfelt, L., . . . Ingelsson, M. (2017). Cognitive function in very old men does not correlate to biomarkers of Alzheimer's disease. BMC Geriatrics, 17(1), Article ID 208.
Open this publication in new window or tab >>Cognitive function in very old men does not correlate to biomarkers of Alzheimer's disease
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2017 (English)In: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 17, no 1, article id 208Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The Alzheimer's disease (AD) brain displays atrophy with amyloid-β (Aβ) and tau deposition, whereas decreased Aβ42 and increased tau are measured in cerebrospinal fluid (CSF). The aim of this study was to relate cognitive performance to the degree of brain atrophy, CSF biomarker levels and neuropathology in a cohort of aged men.

METHODS: Fifty-eight 86-92-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort underwent cognitive testing, brain computed tomography and lumbar puncture. Atrophy was graded with established scales. Concentrations of CSF Aβ42, t-tau and p-tau were measured by ELISA. Thirteen brains were examined post mortem.

RESULTS: Forty-six of the individuals were considered non-demented, whereas twelve were diagnosed with dementia, either at baseline (n = 4) or during follow-up (n = 8). When comparing subjects with and without dementia, there were no differences in the degree of atrophy, although the mini mental state examination (MMSE) scoring correlated weakly with the degree of medial temporal atrophy (MTA) (p = 0.04). Moreover, the CSF biomarker levels did not differ significantly between healthy (n = 27) and demented (n = 8) subjects (median values 715 vs 472 pg/ml for Aβ42, 414 vs 427 pg/ml for t-tau and 63 vs 60 pg/ml for p-tau). Similarly, there were no differences in the biomarker levels between individuals with mild (n = 24) and severe (n = 11) MTA (median values 643 vs 715 pg/ml for Aβ42, 441 vs 401 pg/ml for t-tau and 64 vs 53 pg/ml for p-tau). Finally, the neuropathological changes did not correlate with any of the other measures.

CONCLUSION: In this cohort of aged men only a weak correlation could be seen between cognitive performance and MTA, whereas the various neuroradiological, biochemical and neuropathological measures did not correlate with each other. Thus, AD biomarkers seem to be less informative in subjects of an advanced age.

Keywords
AD biomarkers, Advanced age, Brain atrophy, CSF biomarkers, Cognitive performance, Neuropathology
National Category
Neurology Geriatrics Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-329266 (URN)10.1186/s12877-017-0601-6 (DOI)000410449900002 ()28886705 (PubMedID)
Note

V. Velickaite and V. Giedraitis contributed equally.

Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2017-12-06Bibliographically approved
Skillbäck, T., Delsing, L., Synnergren, J., Mattsson, N., Janelidze, S., Nägga, K., . . . Zetterberg, H. (2017). CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients. Neurobiology of Aging, 59, 1-9
Open this publication in new window or tab >>CSF/serum albumin ratio in dementias: a cross-sectional study on 1861 patients
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2017 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 59, p. 1-9Article in journal (Refereed) Published
Abstract [en]

A connection between dementias and blood-brain barrier (BBB) dysfunction has been suggested, but previous studies have yielded conflicting results. We examined cerebrospinal fluid (CSF)/serum albumin ratio in a large cohort of patients diagnosed with Alzheimer's disease (AD, early onset [EAD, n = 130], late onset AD [LAD, n = 666]), vascular dementia (VaD, n = 255), mixed AD and VaD (MIX, n = 362), Lewy body dementia (DLB, n = 50), frontotemporal dementia (FTD, n = 56), Parkinson's disease dementia (PDD, n = 23), other dementias (other, n = 48), and dementia not otherwise specified (NOS, n = 271). We compared CSF/serum albumin ratio to 2 healthy control groups (n = 292, n = 20), between dementia diagnoses, and tested biomarker associations. Patients in DLB, LAD, VaD, MIX, other, and NOS groups had higher CSF/serum albumin ratio than controls. CSF/serum albumin ratio correlated with CSF neurofilament light in LAD, MIX, VaD, and other groups but not with AD biomarkers. Our data show that BBB leakage is common in dementias. The lack of association between CSF/serum albumin ratio and AD biomarkers suggests that BBB dysfunction is not inherent to AD but might represent concomitant cerebrovascular pathology.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2017
Keywords
CSF/serum albumin ratio, Dementia, Blood-brain barrier, Alzheimer's disease
National Category
Geriatrics
Identifiers
urn:nbn:se:uu:diva-336429 (URN)10.1016/j.neurobiolaging.2017.06.028 (DOI)000411446800001 ()28779628 (PubMedID)
Funder
Swedish Research Council, 2013-2546EU, European Research Council, 681712Knut and Alice Wallenberg FoundationThe Swedish Brain Foundation, FO2015-0021Torsten Söderbergs stiftelseStiftelsen Gamla TjänarinnorKnowledge Foundation, 2014-0298Swedish Association of Local Authorities and Regions
Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2017-12-18Bibliographically approved
Franzon, K., Byberg, L., Sjögren, P., Zethelius, B., Cederholm, T. & Kilander, L. (2017). Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men. Journal of The American Geriatrics Society, 65(9), 1953-1960
Open this publication in new window or tab >>Predictors of Independent Aging and Survival: A 16-Year Follow-Up Report in Octogenarian Men
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2017 (English)In: Journal of The American Geriatrics Society, ISSN 0002-8614, E-ISSN 1532-5415, Vol. 65, no 9, p. 1953-1960Article in journal (Refereed) Published
Abstract [en]

OBJECTIVES: To examine the longitudinal associations between aging with preserved functionality, i.e. independent aging and survival, and lifestyle variables, dietary pattern and cardiovascular risk factors.

DESIGN: Cohort study.

SETTING: Uppsala Longitudinal Study of Adult Men, Sweden.

PARTICIPANTS: Swedish men (n = 1,104) at a mean age of 71 (range 69.4-74.1) were investigated, 369 of whom were evaluated for independent aging 16 years later, at a mean age of 87 (range 84.8-88.9).

MEASUREMENTS: A questionnaire was used to obtain information on lifestyle, including education, living conditions, and physical activity. Adherence to a Mediterranean-like diet was assessed according to a modified Mediterranean Diet Score derived from 7-day food records. Cardiovascular risk factors were measured. Independent aging at a mean age of 87 was defined as lack of diagnosed dementia, a Mini-Mental State Examination score of 25 or greater, not institutionalized, independence in personal activities of daily living, and ability to walk outdoors alone. Complete survival data at age 85 were obtained from the Swedish Cause of Death Register.

RESULTS: Fifty-seven percent of the men survived to age 85, and 75% of the participants at a mean age of 87 displayed independent aging. Independent aging was associated with never smoking (vs current) (odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.05-4.60) and high (vs low) adherence to a Mediterranean-like diet (OR = 2.69, 95% CI = 1.14-6.80). Normal weight or overweight and waist circumference of 102 cm or less were also associated with independent aging. Similar associations were observed with survival.

CONCLUSION: Lifestyle factors such as never smoking, maintaining a healthy diet, and not being obese at age 71 were associated with survival and independent aging at age 85 and older in men.

Keywords
Mediterranean diet, healthy aging, longitudinal, obesity, smoking
National Category
Geriatrics Nutrition and Dietetics
Identifiers
urn:nbn:se:uu:diva-334423 (URN)10.1111/jgs.14971 (DOI)000411060500016 ()28685810 (PubMedID)
Available from: 2017-11-23 Created: 2017-11-23 Last updated: 2018-08-24Bibliographically approved
Sims, R., van der Lee, S. J., Naj, A. C., Bellenguez, C., Badarinarayan, N., Jakobsdottir, J., . . . Schellenberg, G. D. (2017). Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease [Letter to the editor]. Nature Genetics, 49(9), 1373-+
Open this publication in new window or tab >>Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
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2017 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 9, p. 1373-+Article in journal, Letter (Refereed) Published
Abstract [en]

We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 x 10(-4)) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 x 10(-8)) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p. Pro522Arg, P = 5.38 x 10(-10), odds ratio (OR) = 0.68, minor allele frequency (MAF) cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p. Ser209Phe, P = 4.56 x 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p. Arg62His, P = 1.55 x 10(-14), OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer's disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer's disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer's disease.

National Category
Genetics
Identifiers
urn:nbn:se:uu:diva-334927 (URN)10.1038/ng.3916 (DOI)000408672000016 ()28714976 (PubMedID)
Available from: 2017-12-01 Created: 2017-12-01 Last updated: 2017-12-01Bibliographically approved
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