CEREBROSPINAL-FLUID LEVELS OF ALPHA-SECRETASE-CLEAVED SOLUBLE AMYLOIDPRECURSOR PROTEIN MIRROR COGNITION IN A SWEDISH FAMILY WITH ALZHEIMER-DISEASE AND A GENE MUTATION

Objective: To explore the relationship between possible biological mar kers of Alzheimer disease that are related to amyloid metabolism and m ental 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: Cer ebrospinal fluid levels of alpha-secretase cleaved soluble amyloid pre cursor protein (alpha-sAPP), total sAPP, and amyloid beta-peptide were correlated with data on multiple cognitive functions that covered the whole range of human performance. Setting: The Alzheimer's Disease Re search Centre, Department of Clinical Neuroscience, Section of Geriatr ic Medicine, Karolinska Institute, Huddinge University Hospital, Huddi nge, Sweden. Result: There were highly significant linear correlations between low levels of alpha-sAPP and poor performance on neuropsychol ogical tests that assessed intelligence, verbal and visuospatial funct ions, memory, and attention. Within the group of nonmutation carriers, significant correlations were also obtained between the levels of alp ha-sAPP and cognitive functions. A less striking association was seen between the levels of total sAPP and cognition. No association was fou nd between the levels of amyloid beta-peptide and cognition. Conclusio ns: The strong relationship between alpha-sAPP levels and cognition in both patients with Alzheimer disease and normal-aging persons may imp ly that alpha-sAPP is involved in basic protective brain processes. Al ternatively, less amyloid beta-peptide amounts are produced, leading t o diminished plaque formation, when alpha-sAPP is generated.