Physiological clearance of Aβ by spleen and splenectomy aggravates Alzheimer‐type pathogenesis

Abstract Background Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer’s disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer type. Their prognosis, as well as predictors of clinical progression, are not fully understood. The aim of this study was to explore the associations of cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau) and other characteristics, including modifiable vascular factors, with the risk of progression to dementia among patients with MCI and normal CSF Aβ42. Methods Three hundred eighteen memory clinic patients with CSF and clinical data, and at least 1-year follow-up, were included. Patients had normal CSF Aβ42 levels based on clinical cut-offs. Cox proportional hazard models with age as time scale and adjusted for sex, education, and cognition (Mini-Mental State Examination) were used to investigate predictors of progression to dementia and Alzheimer-type dementia. Potential predictors included CSF biomarkers, cognitive performance (verbal learning and memory), apolipoprotein E (APOE) ε4 genotype, medial temporal lobe atrophy, family history of dementia, depressive symptoms, and vascular factors, including the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score. Predictive performance of patient characteristics was further explored with Harrell C statistic. Results Lower normal Aβ42 and higher total tau and phosphorylated tau were associated with higher dementia risk, and the association was not driven by Aβ42 values close to cut-off. Additional predictors included poorer cognition, APOE ε4 genotype, higher systolic blood pressure, and lower body mass index, but not the CAIDE dementia risk score. Aβ42 individually and in combination with other CSF biomarkers improved the risk prediction compared to age and cognition alone. Medial temporal lobe atrophy or vascular factors did not increase the predictive performance. Conclusions Possibility of underlying AD pathology and increased dementia risk should not be ruled out among MCI patients with CSF Aβ42 within the normal range. While cut-offs may be useful in clinical practice to identify high-risk individuals, personalized risk prediction tools incorporating continuous biomarkers may be preferable among individuals with intermediate risk. The role of modifiable vascular factors could be explored in this context.

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Thyrotropin response to thyrotropin-releasing hormone in patients with dementia of the Alzheimer type

Biological Psychiatry ◽

10.1016/0006-3223(93)90293-m ◽

1993 ◽

Vol 33 (4) ◽

pp. 267-271 ◽

Cited By ~ 7

Author(s):

Marilyn Albert ◽

Michael Jenike ◽

Ralph Nixon ◽

Kenneth Nobel

Keyword(s):

Thyrotropin Releasing Hormone ◽

Alzheimer Type ◽

Releasing Hormone

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Alzheimer disease detection and analysis using P3 component of ERP in Alzheimer type dementia

2001 Conference Proceedings of the 23rd Annual International Conference of the IEEE Engineering in Medicine and Biology Society ◽

10.1109/iembs.2001.1019109 ◽

2005 ◽

Author(s):

E.H. Park ◽

S.Y. Cho ◽

J.W. Kim ◽

W.W. Whang ◽

H.T. Kim

Keyword(s):

Alzheimer Disease ◽

Disease Detection ◽

Alzheimer Type ◽

Alzheimer Type Dementia ◽

P3 Component

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Impaired Physical Performance and the Assessment of Dementia of the Alzheimer Type

Alzheimer Disease & Associated Disorders ◽

10.1097/01.wad.0000127441.77570.f3 ◽

2004 ◽

Vol 18 (3) ◽

pp. 112-119 ◽

Cited By ~ 15

Author(s):

Kamini R Shah ◽

David Carr ◽

Catherine M Roe ◽

J Philip Miller ◽

Mary Coats ◽

...

Keyword(s):

Physical Performance ◽

Alzheimer Type

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