Clinical features of rapidly progressive Alzheimer's disease.
OBJECTIVE
To characterize clinical features, CSF biomarkers and genetic polymorphisms of patients suffering from a rapidly progressing subtype of Alzheimer's dementia (rpAD).


METHODS
Retrospective analyses of 32 neuropathologically confirmed cases differentially diagnosed as AD out of a group with rapidly progressive dementia. CSF biomarkers (14-3-3, tau, beta-amyloid 1-42) and genetic markers (PRNP codon 129, apolipoprotein E, ApoE, polymorphism) were determined.


RESULTS
Median survival was 26 months, age at onset 73 years. Biomarkers: mean beta-amyloid 1-42: 266 pg/ml, median tau: 491 pg/ml, 14-3-3 positive: 31%. Genetic polymorphisms showed a predominance of methionine homozygosity at PRNP codon 129 and a low frequency of ApoE4 (38%, no homozygous patients). Thirty-five symptoms were studied. Frequent symptoms were myoclonus (75%), disturbed gait (66%) and rigidity (50%).


CONCLUSIONS
rpAD is associated with a diversity of neurological signs even able to mimic Creutzfeldt-Jakob disease. Biomarkers and genetic profile differ from those seen in classical AD. The findings on biomarkers, symptomatology and genetics may aid the differential diagnostic process.
Schmidt
Christian
C
Department of Neurology, Hospital of the Georg August University Goettingen, Goettingen, Germany.
Redyk
Katharina
K
Meissner
Bettina
B
Krack
Lennart
L
von Ahsen
Nico
N
Roeber
Sigrun
S
Kretzschmar
Hans
H
Zerr
Inga
I
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D053327:Apolipoprotein E4 / Q000235:genetics; D001057:Apolipoproteins E / Q000235:genetics; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D003062:Codon; D018450:Disease Progression; D005260:Female; D005684:Gait; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology; D009207:Myoclonus / Q000209:etiology; D010446:Peptide Fragments / Q000134:cerebrospinal fluid; D011110:Polymorphism, Genetic; D000072002:Prion Proteins; D011328:Prions / Q000235:genetics; D012189:Retrospective Studies; D016019:Survival Analysis; D013997:Time Factors; D014633:Valine; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D015415:Biomarkers; D003062:Codon; C512656:PRNP protein, human; D010446:Peptide Fragments; D000072002:Prion Proteins; D011328:Prions; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D008715:Methionine; D014633:Valine