Cerebrospinal fluid levels of alpha-secretase-cleaved soluble amyloid precursor protein mirror cognition in a Swedish family with Alzheimer disease and a gene mutation.
OBJECTIVE
To explore the relationship between possible biological markers of Alzheimer disease that are related to amyloid metabolism and mental functions.


METHODS
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.


METHODS
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.


METHODS
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.
Almkvist
O
O
Department of Clinical Neuroscience, Karolinska Institute Huddinge University Hospital, Stockholm, Sweden.
Basun
H
H
Wagner
S L
SL
Rowe
B A
BA
Wahlund
L O
LO
Lannfelt
L
L
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000134:cerebrospinal fluid / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D003071:Cognition; D010450:Endopeptidases / Q000378:metabolism*; D005260:Female; D005796:Genes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D012995:Solubility
D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human