Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation
O. Almkvist, H. Basun, S. L. Wagner, B. A. Rowe, L. O. Wahlund and L. Lannfelt
Department of Clinical Neuroscience, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
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 alpha-secretase cleaved soluble amyloid precursor 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 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
alpha-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 alpha-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
beta-peptide and cognition. CONCLUSIONS: The strong relationship between
alpha-sAPP levels and cognition in both patients with Alzheimer disease and
normal-aging persons may imply that alpha-sAPP is involved in basic
protective brain processes. Alternatively, less amyloid beta-peptide
amounts are produced, leading to diminished plaque formation, when
alpha-sAPP is generated.
