P4-354: Baseline CSF BETA-AMYLOID 42 correlates with ApoE genotype and baseline cognitive status in a phase II avagacestat predementia Alzheimer's disease study

Abstract Background Lipocalin-2 is a glycoprotein that is involved in various physiological and pathophysiological processes. In the brain, it is expressed in response to vascular and other brain injury, as well as in Alzheimer’s disease in reactive microglia and astrocytes. Plasma Lipocalin-2 has been proposed as a biomarker for Alzheimer’s disease but available data is scarce and inconsistent. Thus, we evaluated plasma Lipocalin-2 in the context of Alzheimer’s disease, differential diagnoses, other biomarkers, and clinical data. Methods For this two-center case-control study, we analyzed Lipocalin-2 concentrations in plasma samples from a cohort of n = 407 individuals. The diagnostic groups comprised Alzheimer’s disease (n = 74), vascular dementia (n = 28), other important differential diagnoses (n = 221), and healthy controls (n = 84). Main results were validated in an independent cohort with patients with Alzheimer’s disease (n = 19), mild cognitive impairment (n = 27), and healthy individuals (n = 28). Results Plasma Lipocalin-2 was significantly lower in Alzheimer’s disease compared to healthy controls (p < 0.001) and all other groups (p < 0.01) except for mixed dementia (vascular and Alzheimer’s pathologic changes). Areas under the curve from receiver operation characteristics for the discrimination of Alzheimer’s disease and healthy controls were 0.783 (95%CI: 0.712–0.855) in the study cohort and 0.766 (95%CI: 0.627–0.905) in the validation cohort. The area under the curve for Alzheimer’s disease versus vascular dementia was 0.778 (95%CI: 0.667–0.890) in the study cohort. In Alzheimer’s disease patients, plasma Lipocalin2 did not show significant correlation with cerebrospinal fluid biomarkers of neurodegeneration and AD-related pathology (total-tau, phosphorylated tau protein, and beta-amyloid 1-42), cognitive status (Mini Mental Status Examination scores), APOE genotype, or presence of white matter hyperintensities. Interestingly, Lipocalin 2 was lower in patients with rapid disease course compared to patients with non-rapidly progressive Alzheimer’s disease (p = 0.013). Conclusions Plasma Lipocalin-2 has potential as a diagnostic biomarker for Alzheimer’s disease and seems to be independent from currently employed biomarkers.

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Interaction Between APOE Genotype and Diabetes in Longevity

Journal of Alzheimer s Disease ◽

10.3233/jad-210125 ◽

2021 ◽

pp. 1-8

Author(s):

Mitsuru Shinohara ◽

Kaoru Suzuki ◽

Guojun Bu ◽

Naoyuki Sato

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apolipoprotein E ◽

Interactive Effect ◽

Apoe Genotype ◽

Potential Interaction ◽

Cognitive Status ◽

Diabetic Status ◽

Clinical Records ◽

Harmful Effects

Background: While both apolipoprotein E (APOE) genotype and diabetes affect longevity as well as Alzheimer’s disease, their relationship remains to be elucidated. Objective: The current study investigated the potential interaction between diabetes and APOE for lifespan and their relationship with cognitive status. Methods: We reviewed the National Alzheimer’s Coordinating Center (NACC) dataset, which documents longitudinally clinical records of 24,967 individuals with APOE genotype and diabetic status. Results: Diabetes was associated with shorter lifespan in APOE3 carriers (n = 12,415, HR = 1.29, 95%CI = 1.17–1.42, p < 0.001) and APOE2 carriers (n = 2,390, HR = 1.37, 95%CI = 1.10–1.69, p = 0.016), while such associations were weaker and not significant in APOE4 carriers (n = 9,490, HR = 1.11, 95%CI = 0.99–1.24, p = 0.162). As there is a significant interactive effect of cognitive status and diabetes on lifespan (p < 0.001), we stratified subjects by cognitive status and observed persistent APOE-dependent harmful effects of diabetes in nondemented individuals but not demented individuals. Notably, questionnaire-based activity status, with which we previously observed an association between APOE genotype and longevity, was also significantly affected by diabetes only in non-APOE4 carriers. Conclusion: The effects of diabetes on longevity vary among APOE genotype. These effects are observed in nondemented individuals and are potentially associated with activity status during their lifespan.

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O4-11-05: A PHASE II STUDY TO EVALUATE THE EFFICACY AND SAFETY OF PLASMA REPLACEMENT WITH 5% ALBUMIN IN BETA-AMYLOID PEPTIDE CLEARANCE IN CEREBROSPINAL FLUID, AND ITS EFFECTS IN PATIENTS WITH MILD-MODERATE ALZHEIMER'S DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2014.04.449 ◽

2014 ◽

Vol 10 ◽

pp. P274-P274

Author(s):

Mercè Boada-Rovira ◽

Oscar Lopez ◽

Laura Núñez ◽

Pilar Ortiz ◽

Fernando Anaya ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Phase Ii ◽

Phase Ii Study ◽

Beta Amyloid ◽

Amyloid Peptide ◽

Efficacy And Safety ◽

Beta Amyloid Peptide

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CSF beta-amyloid, cognition, and APOE genotype in Alzheimer's disease

Neurology ◽

10.1212/wnl.52.3.547 ◽

1999 ◽

Vol 52 (3) ◽

pp. 547-547 ◽

Cited By ~ 43

Author(s):

S. C. Samuels ◽

J. M. Silverman ◽

D. B. Marin ◽

E. R. Peskind ◽

S. G. Younki ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Apoe Genotype ◽

Beta Amyloid

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Case Studies in Dementia-Related Anxiety

GeroPsych ◽

10.1024/1662-9647/a000243 ◽

2020 ◽

pp. 1-6

Author(s):

Molly Maxfield ◽

Jennifer R. Roberts ◽

JoAnna Dieker

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Social Withdrawal ◽

Cognitive Status ◽

Generalized Anxiety ◽

Neurocognitive Disorder ◽

High Genetic Risk ◽

Disease Case ◽

Negative Perceptions

Abstract. Two clients seeking neuropsychological assessment reported anxiety about their cognitive status. We review the cases to increase our understanding of factors contributing to dementia-related anxiety. Case 1 met the criteria for mild neurocognitive disorder; the client’s memory was impaired, and she had a high genetic risk for Alzheimer’s disease. The client reported anxiety about negative perceptions of quality of life among individuals diagnosed with Alzheimer’s disease. Case 2 did not meet the criteria for a neurocognitive disorder. Anxiety about this client’s cognitive status appeared attributable to generalized anxiety disorder, given his anxiety about diverse topics. Both clients reported embarrassment about forgetfulness and social withdrawal. Dementia-related anxiety is believed to be relatively common, to exist on a continuum, to have unique social implications, and to stem from various sources, necessitating differing interventions.

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