A study involving 4,050 people with late-onset Alzheimer's disease (mean age 80) has classified them into six groups based on their cognitive functioning at the time of diagnosis. A genetic study found two of the groups showed strong genetic associations.
The participants received cognitive scores in four domains: memory, executive functioning, language, and visuospatial functioning. The largest group (39%) had scores in all four domains that were fairly close to each other. The next largest group (27%) had memory scores substantially lower than their other scores. Smaller groups had language scores substantially lower than their other scores (13%), visuospatial functioning scores substantially lower than their other scores (12%), and executive functioning scores substantially lower than their other scores (3%). There were 6% who had two domains that were substantially lower than their other scores.
One group showed a very strong genetic association with 33 single nucleotide polymorphisms (SNPs) — this effect was stronger than the strongest effects found by an earlier and much larger international consortium study where Alzheimer's disease was treated as a single condition.
The memory group had a particularly strong relationship with the APOE e4 allele.
The participants were mostly white (92%) and 61% were female.
The finding is supported by another study using brain tissue from deceased patients with rare and common forms of Alzheimer’s, and from those who didn’t have the disease. The study showed that different genes are associated with different types of brain damage.
Those with the genes implicated in early-onset Alzheimer's (APP, PSEN1, and PSEN2) showed lower numbers of neurons and higher numbers of astrocytes than people who had Alzheimer’s but didn’t carry those mutations.
A similar pattern was found in patients with APOE4. However, carriers of TREM2 showed less neuronal loss and more damage to glial cells.
(2018). Genetic data and cognitively defined late-onset Alzheimer’s disease subgroups.
Molecular Psychiatry. 1 - 10.
(2018). Genetic variants associated with Alzheimer’s disease confer different cerebral cortex cell-type population structure.
Genome Medicine. 10(1), 43.