Long telomeres can be linked to poorer memory

The end portions of chromosomes, telomeres, are important in protecting the genes inside. Every time a cell divides, these telomeres become shorter. After multiple cell divisions, the telomeres become so short that the cell either self-dies or wind up in an aged, resting stage. Measurement of telomere lengths therefore provides information about how many times the cells has divided in the past.

This new study is part of the major Betula Project, which, according to the Swedish Research Council, is one of the ten strongest research settings in Sweden and has the goal of studying how the memory changes during aging. It comprises 427 non-demented individuals between the ages of 41 and 81 years. The scientists studied whether individuals with different forms of apolipoprotein E (APOE) have different telomere lengths in their blood cells and whether variations in telomere length is linked to memory capacity, assessed with the help of memory tests. Previous research has described the connection between the form of APOE 4 and cardiovascular disease and dementia. It has also been shown that this variant increases the risk of a type of memory degradation that is most pronounced in older individuals without dementia. This is a degradation of memory in the so-called episodic memory system, which, in simple terms, has the assignment of remembering episodes in life.

In summary the newly published study shows that individuals with APOE 4 have longer telomeres than those with other APOE variants. It was also found that the difference in telomere length between APOE 4 and other APOE variants increased the younger the individuals compared were. In the group that had the variant APOE 4 the individuals with the longest telomeres performed less well on episodic memory tests but not on other tests.

The APOE protein plays a central role in transporting and metabolizing blood fats, but the various forms also appear to have different effects on other processes in the body. The 4 variant is linked with worse blood fats, more inflammation, and increased oxidative stress compared with the 2 and 3 variants. It has previously been shown that both inflammation and oxidative stress lead to shorter telomere length. It was therefore surprising that individuals with the 4 variant had longer telomeres than individuals with the other APOE forms. The longer telomeres support the notion that the cells have undergone a lower number of cell divisions and that the differences in length arose at some time prior to the lower age limit for the study. Such reduced cell division early in life may be an explanation for the worse episodic memory of people with the 4 variant compared with that of individuals with other variants. More studies are needed to confirm these findings and to determine through what mechanisms long telomeres are associated with poorer episodic memory and with any other possible APOE 4-associated processes in the body.

The researchers behind the study are Karl-Fredrik Norrback, Rolf Adolfsson, Göran Roos, and Lars Nyberg at Umeå University; Lars-Göran Nilsson, Stockholm University; and Thomas Karlsson, Linköping University, as well as doctoral candidate Mikael Wikgren. The project coordinator Annelie Nordin has also been important for the conducting of the study.

For more information, please contact: Karl-Fredrik Norrback, MD, PhD, Dept. of Clinical Science, Division of Psychiatry, Umeå University, Mobile phone: +46 (0)70-441 5904, e-mail: karl-fredrik.norrback@psychiat.umu.se

Pressofficer Hans Fällman; hans.fallman@adm.umu.se; +46-70 691 28 29

Reference: Wikgren M, Karlsson T, Nilbrink T, Nordfjäll K, Hultdin J, Sleegers K, Van Broeckhoven C, Nyberg L, Roos G, Nilsson LG, Adolfsson R, Norrback KF APOE epsilon4 is associated with longer telomeres, and longer telomeres among epsilon4 carriers predicts worse episodic memory, Neurobiology of Aging, 2010 Apr 13 (10.1016/j.neurobiolaging.2010.03.004).