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May 1997

Cerebrospinal Fluid Levels of α-Secretase—Cleaved Soluble Amyloid Precursor Protein Mirror Cognition in a Swedish Family With Alzheimer Disease and a Gene Mutation

Author Affiliations

From the Departments of Clinical Neuroscience and Family Medicine, Division of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden (Drs Almkvist, Basun, Wahlund, and Lannfelt), and SIBIA Neurosciences Inc, La Jolla, Calif (Dr Wagner and Mr Rowe).

Arch Neurol. 1997;54(5):641-644. doi:10.1001/archneur.1997.00550170111022

Objective:  To explore the relationship between possible biological markers of Alzheimer disease that are related to amyloid metabolism and mental functions.

Participants:  Twelve individuals from a Swedish family with Alzheimer disease and a double mutation at codons 670/671 of the amyloid precursor protein gene participated in the study.

Design:  Cerebrospinal fluid levels of α-secretase cleaved soluble amyloid precursor protein (α-sAPP), total sAPP, and amyloid β-peptide were correlated with data on multiple cognitive functions that covered the whole range of human performance.

Setting:  The Alzheimer's Disease Research Centre, Department of Clinical Neuroscience, Section of Geriatric Medicine, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden.

Results:  There were highly significant linear correlations between low levels of α-sAPP and poor performance on neuropsychological tests that assessed intelligence, verbal and visuospatial functions, memory, and attention. Within the group of nonmutation carriers, significant correlations were also obtained between the levels of α-sAPP and cognitive functions. A less striking association was seen between the levels of total sAPP and cognition. No association was found between the levels of amyloid β-peptide and cognition.

Conclusions:  The strong relationship between α-sAPP levels and cognition in both patients with Alzheimer disease and normal-aging persons may imply that α-sAPP is involved in basic protective brain processes. Alternatively, less amyloid β-peptide amounts are produced, leading to diminished plaque formation, when α-sAPP is generated.