Amyloid burden similar among those with Alzheimer's disease, Down syndrome

Amyloid positron emission tomography scan changes were similar between individuals with autosomal dominant Alzheimer’s disease and those with Down syndrome, researchers reported in The Lancet Neurology.

Down syndrome, which is caused by full or partial triplication of chromosome 21, is one of the most common genetic disorders. Because of triplication, those with Down syndrome have an extra copy of the APP gene, which overproduces amyloid beta, Anna H. Boerwinkle, BS, of the Ances Bioimaging Laboratory at Washington University School of Medicine in St. Louis, and colleagues wrote.

Boerwinkle and colleagues sought to assess whether the timing and spatial distribution of amyloid accumulation differs between those with autosomal dominant AD and those with Down syndrome.

The researchers conducted a cross-sectional study of participants aged 25 years and older with Down syndrome and sibling controls who had MRI and amyloid PET scans in the Alzheimer’s Biomarker Consortium-Down Syndrome study. In addition, carriers of autosomal dominant AD disease genetic mutations and family controls were included.

Both groups of controls were combined into a single control group. Carriers of the Alzheimer’s mutation and their non-carrier familial controls received genetic testing to determine PSEN1, PSEN2 or APP mutation status. APOE genotype was determined through blood samples. Cerebrospinal fluid samples were collected from those who agreed to undergo lumbar puncture.

There was a total of 192 participants with Down syndrome and 33 sibling controls, as well as 265 carriers of autosomal dominant AD mutations and 169 non-carrier familial controls.

PET amyloid centiloid and CSF alpha beta 42/40 were negatively correlated in carriers of autosomal dominant AD mutations (n = 216; –0.565) and in those with Down syndrome (n = 32; –0.801).

There was no difference in global PET amyloid burden between asymptomatic people with Down syndrome (mean, 18.8 centiloids) and asymptomatic mutation carriers (mean, 24.61 centiloids), as well as between symptomatic people with Down syndrome (mean, 77.25 centiloids) and symptomatic mutation carriers (mean, 69.15 centiloids).

Amyloid deposition was elevated significantly earlier in mutation carriers than in those with Down syndrome (years to symptom onset, –23 vs. –17.5), which was primarily driven by PSEN1 mutations.

Early amyloid accumulation occurred in the striatal and cortical regions for both mutation carriers (n = 265) and in those with Down syndrome (n = 128).

“Despite minor differences, amyloid PET changes were similar between people with autosomal dominant Alzheimer’s disease vs. Down syndrome and strongly supported early amyloid dysregulation in individuals with Down syndrome,” Boerwinkle and colleagues wrote. “Individuals with Down syndrome aged at least 35 years might benefit from early intervention and warrant future inclusion in clinical trials, particularly given the relatively high incidence of Down syndrome.”