Table 1 ∣.
Similarities and differences between sporadic and familial Alzheimer disease
| Feature | ADAD | EOAD | LOAD |
|---|---|---|---|
| Age at onset (years) | <50 | <65 | ≥65 |
| Sex distribution75 | Female = male | Female = male | Female > male |
| Episodic memory loss | Earlya | Earlya | Earlya |
| Atypical signs and signals4,76 | Common | Higher frequency of dysexecutive symptoms and atypical presentation than LOAD | Uncommon |
| Genetic contributions | Autosomal dominant | Probably polygenic | Probably polygenic |
| Frequency of APOE4 carriers (%)28,77-80 | Up to 30 | ~60 (except for low frequency in atypical cases) | ~60 |
| Neuropathological hallmarks | Plaques and tangles | Plaques and tangles | Plaques and tangles |
| Structure of amyloid-β filaments30 | Type II | Unreported | Type I |
| Pattern of amyloid-β spread81,82 | Neocortex first; 10–20% with striatal origin | Neocortex first | Neocortex first |
| Presence of plaque variations in addition to the common neuritic and diffuse plaques83,84 | Cotton-wood type | Subset of cases with coarse plaques | Rare cases with coarse plaques |
| Initial tau accumulationb (refs. 85,86) | Unknown | Subcortical nuclei belonging to the neuromodulatory subcortical systemc | Subcortical nuclei belonging to the neuromodulatory subcortical systemc |
| First regional evidence of PET signald (refs. 87,88) | Precuneus | Mesial temporal region | Mesial temporal region |
| Tau burden31,89,90 | Higher in the striatum than in sporadic cases | Higher in cortical areas than in LOAD | Higher in limbic areas than in ADAD and EOAD |
| Rate of brain atrophy81 | Fast | Fast | Slow |
| Highest magnitude of brain atrophy91-93 | Neocortical and medial temporal | Neocortical > medial temporal | Medial temporal > neocortical |
| CSF assays of amyloid-β42; amyloid-β40; tau; phosphorylated tau181 (ref. 81) | Reduced; reduced; increased; increased | Reduced; reduced; increased; increased | Reduced; reduced; increased; increased |
ADAD, autosomal dominant Alzheimer disease; CSF, cerebrospinal fluid; EOAD, sporadic early-onset (<65 years of age) AD; LOAD, sporadic late-onset AD. a A subset of ADAD manifests spastic paraparesis and behavioural presentations preceding memory decline. About 5% of sporadic cases manifest AD pathology with a non-amnestic presentation, the so-called atypical AD cases. b According to post-mortem studies. c For more details about the neuromodulatory subcortical system, see refs. 85,86. d PET has a low resolution to capture most subcortical structures.