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Novel Alzheimer’s Biomarker for Early Detection

Changes in the spinal fluid during middle age may identify people at risk of developing Alzheimer's disease later in life.

In that the presymptomatic stage of Alzheimer’s disease provides an opportunity for early intervention, the scientists have focused on identifying you biomarkers to assist with identifying at-risk populations. Anne Fagan, from the Washington University School of Medicine (Missouri, USA), and colleagues studied a group of 169 cognitively normal men and women, ages 45 to 75 years when they entered the study – and followed them for 10 years. Each subject received a complete clinical, cognitive imaging and cerebrospinal fluid biomarker analysis every three years, with a minimum of two evaluations.  At the participants’ initial assessments, researchers divided them into three age groups: early-middle age (45-54); mid-middle age (55- 64); and late-middle age (65-74).  The researchers tracked changes in: amyloid beta 42, a protein that is the principal ingredient of Alzheimer’s plaques; tau, a structural component of brain cells that increases in the cerebrospinal fluid as Alzheimer’s disease damages brain cells; YKL-40, a newly recognized protein that is indicative of inflammation and is produced by brain cells; and the presence of amyloid plaques in the brain, as seen via amyloid PET scans.  The team observed that drops in amyloid beta 42 levels in the cerebrospinal fluid among cognitively normal participants ages 45-54 are linked to the appearance of plaques in brain scans years later. They also found that tau and other biomarkers of brain-cell injury increase sharply in some individuals as they reach their mid-50s to mid-70s, and YKL-40 rises throughout the age groups focused on in the study. Writing that: “Longitudinal [cerebrospinal fluid] biomarker patterns consistent with [Alzheimer’s disease] are first detectable during early middle age and are associated with later amyloid positivity and cognitive decline,” the study authors submit that: “such measures may be useful for targeting middle-aged, asymptomatic individuals for therapeutic trials designed to prevent cognitive decline.”

Sutphen CL, Jasielec MS, Shah AR, Macy EM, Xiong C, Vlassenko AG, Benzinger TL, Stoops EE, Vanderstichele HM, Brix B, Darby HD, Vandijck ML, Ladenson JH, Morris JC, Holtzman DM, Fagan AM.  “Longitudinal Cerebrospinal Fluid Biomarker Changes in Preclinical Alzheimer Disease During Middle Age.”  JAMA Neurol. 2015 Jul 6.

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