Glossary

Acetylcholine A neurotransmitter whose levels are decreased in Alzheimer’s disease.

Acetylcholinesterase inhibitors Drugs commonly used in Alzheimer’s disease. They prevent the breakdown of the neurotransmitter acetylcholine and therefore increase levels. They include donepezil, rivastigmine and galantamine.

Agrammatism A term used to describe the symptom of impaired grammar. This may be impaired in speech production or speech comprehension. When producing speech simple words like ‘the’, ‘and’ or ‘of’ might be missing, or the person might use the wrong tense. When listening to speech people may have difficulty understanding complex sentences.

Allele One of the two copies of a gene in every cell.

Anomia Difficulty with naming things.

Alzheimer’s disease The most common type of dementia, characterized by impaired memory in the early stages. It is a neurodegenerative illness with amyloid plaques and neurofibrillary tangles seen in the brain at post mortem.

Amyotrophic lateral sclerosis or ALS A disease in which the nerve cells controlling movement die.  Also known as motor neuron disease.

Aphasia Impairment of language skills.

Apraxia Difficulty performing complex movements.

Apraxia of speech Impaired articulation of speech because of difficulty planning speech production.

Agnosia Difficulty recognizing of objects.

Associative agnosia Difficulty recognizing objects because of loss of knowledge about them.

Autosomal dominant This describes a type of genetic inheritance, or how a trait or disease is passed from one generation to another. There are two copies of each gene in every cell. A disease is autosomal dominant when only one copy of the gene needs to be faulty to cause the disease. This means that children of someone with an autosomal dominant disease have a 50% risk of developing the disease. All of the known genes that cause FTD have autosomal dominant inheritance.

Autosomal recessive This describes a type of genetic inheritance, or how a trait or disease is passed from one generation to another. There are two copies of each gene in every cell. A disease is autosomal recessive when both copies of the gene need to be faulty to cause the disease.

Axial rigidity This describes the symptom of stiffness in the torso (in contrast with limb rigidity which affects the arms and legs). It is a feature of progressive supranuclear palsy.

Behavioural variant FTD or bvFTD One of the main FTD clinical syndromes, presenting with a change in personality and abnormal behaviour.

Bradykinesia This describes the symptom of slowness of movement. It is a feature of the parkinsonian disorders.

C9ORF72 This is the name of a gene found on chromosome 9. Abnormalities of this gene are a major cause of genetic FTD.

Cerebrospinal fluid or CSF This is the fluid surrounding the brain and spinal cord. A sample can be taken for testing by performing a lumbar puncture or spinal tap. Measurement of different proteins in the CSF are being tested as ways of improving the diagnosis of FTD.

Chromosome DNA is organised into structures called chromosomes. There are 23 pairs in each cell in humans, called 1 to 22 and the sex chromosomes called X and Y.

Chromatin modifying protein 2B or CHMP2B This is the name of a gene found on chromosome 3. Mutations in this gene are a rare cause of FTD, sometimes known as FTD-3. Virtually all people with FTD-3 are from a single family in the Jutland area of Denmark.

Corticobasal degeneration or CBD A term used now most frequently to mean a specific type of tau pathology found at post mortem. CBD pathology is most commonly associated with the corticobasal syndrome or CBS, although other clinical syndromes seen with CBD include PNFA, PSP and bvFTD. Note that some people still use the term CBD to mean the same thing as the clinical syndrome of CBS.

Corticobasal syndrome or CBS This is the name for a clinical syndrome, part of the FTD spectrum of disorders. Symptoms of CBS include stiffness of the muscles and slowness of movements more on one side of the body than the other, known as rigidity and bradykinesia. Occasional brief jerking of the muscles, or myoclonus, may occur. People may also have greater difficulty co-ordinating particular movements, known as limb apraxia.

Default mode network or DMN A network of brain regions which share many connections and functions. The DMN includes brain regions in the frontal, parietal and temporal regions of the brain. The specific relevance of the DMN for FTD is still debated, however DMN changes have been linked closely with Alzheimer’s disease.

Dementia A term meaning progressive impairment of thinking that has started in adult life. The most common form is Alzheimer’s disease. Apart from FTD other common dementias are vascular dementia and Dementia with Lewy Bodies. Dementia is called young or early onset if it starts before the age of 65.

DNA A molecule found in cells that codes for our genetic information. The code is made up of a sequence of letters or bases, of which there are four different types called A, G, C and T. There are around three million bases in total in each cell. DNA is organized into chromosomes.

Dysphagia Difficulty with swallowing.

Executive function This is a term for a group of different cognitive functions including planning, problem solving and decision making. The frontal lobes play a large part in controlling these functions. In bvFTD executive dysfunction tends to be the first cognitive problem.

Expansion An abnormal part of a gene where there are extra letters inserted in the code. In C9ORF72 there is a hexanucleotide expansion, meaning that six letters are repeated multiple times. The six letters are GGGGCC and can be repeated over a thousand times in people with FTD compared to less than thirty in people without FTD.

Frontotemporal lobar degeneration or FTLD A term used often to mean the same thing as FTD. It is also sometimes used to refer specifically to the pathology of FTD.

Familial FTD This refers to FTD that runs in families, in other words is inherited from parent to child.

FTDP-17 This stands for frontotemporal dementia with parkinsonism linked to chromosome 17, and is commonly used as another term for FTD associated with mutations in the MAPT gene.

Fused in sarcoma or FUS This is one of the three proteins found in cells at post mortem in people with FTD. There are three subtypes called atypical FTLD-ubiquitin or aFTLDU, neuronal intermediate filament inclusion disease or NIFID and basophilic inclusion body disease or BIBD. Patients with FUS pathology often have a very young onset in their 30’s or 40’s.

Gene A part of DNA which forms a code for the production of a particular protein. Humans have around 30,000 different genes.

Genetic counselling The process which people who are at risk of a genetic disorder go through before having a genetic test.

Genome All the genes that make up a person or organism.

Genome-wide association study or GWAS GWAS identify variations in genes that occur more often in people with a specific disease.  These genetic changes do not cause the disease, but can increase someone’s risk of developing a certain disease during their lifetime.

Glia These are non-neuronal cells found in the brain, that provide support to neurons and are involved in processes such as inflammation.

Induced pluripotent stem cell or iPSC A type of stem cell that has been made by reprogramming another type of cell such as a fibroblast or skin cell.

Limb apraxia Difficulty performing complex movements with the arms or legs.

Lumbar puncture Also called a spinal tap, this is a medical procedure where CSF is taken by inserting a needle into the lower part of the spine.

Magnetic resonance imaging or MRI A type of brain scan often used in the diagnosis of FTD.

Microtubule-associated protein tau or MAPT This is the name given to the gene coding for the microtubule-associated protein tau. Mutations in this gene cause FTD.

Microtubules These form part of the cytoskeleton – a cell scaffolding that provides the cell with internal support and helps it to maintain its structure and shape.  They also act as train tracks for the cell, providing a network on which other components of the cell can move around.

Mitochondria These are the cells power stations.  They convert energy into forms that are usable by the cell, allowing cells to move, divide, synthesise proteins etc.

Motor neuron disease A disorder of the nerve cells or neurons that control movement. Also called amyotrophic lateral sclerosis.

Mutation This is the name given to an abnormality in a gene, usually a change in the sequence of letters in the code. These can be very small changes such as point mutations, where one letter is changed for another, insertions, where an extra letter is added in, or deletions where one letter is missing. They can also be large changes, where whole parts of genes are duplicated or deleted.

Myoclonus This describes brief jerks of the limbs or other parts of the body.

Neurodegenerative A term for diseases of the brain and nervous system caused by loss or degeneration of cells.

Neuroleptic drugs These are also sometimes called antipsychotics as they are the drugs used in psychotic disorders such as schizophrenia. They include drugs like haloperidol, risperidone, olanzapine and quetiapine.

Neuron Neurons are a type of cell found in the brain that process and transmit information to other neurons by electrical and chemical signals.  In FTD, the neurons of the frontal and temporal lobes of the brain die, leading to many of the symptoms.

Nucleus The nucleus is the part of the cell where the DNA is located.

Neurofibrillary tangles or NFTs These are abnormal collections of tau protein seen in the brains of some patients with FTD.

Neurotransmitter Chemicals which transmit signals from one neuron to another at the synapse.

Orofacial apraxia Difficulty performing complex movements of the mouth or face.

Parkinsonian disorders Diseases in which people have bradykinesia and rigidity, often also called akinetic-rigid disorders or parkinsonism. It includes Parkinson’s disease, corticobasal syndrome, progressive supranuclear palsy and multiple system atrophy.

Parkinsonism A term used to mean the same thing as parkinsonian disorders.

Parkinson’s disease The most common parkinsonian disorder. Symptoms include a tremor in the arms, usually seen in the hand at rest on one side first, as well as bradykinesia and rigidity.

Penetrance This describes how many people who have a mutation in a gene develop symptoms. If all people do this is called complete penetrance. However some disorders have incomplete penetrance such that not everyone carrying an abnormal gene will develop symptoms.

Perry syndrome This is a rare TDP disorder which is associated with mutations in the gene dynactin or DCTN1. It is a parkinsonian disorder with other symptoms including difficulty breathing. People may also develop abnormal behaviour similar to bvFTD.

Phosphorylation A chemical modification to proteins that can act as a switch to turn a protein on or off.  In FTD, many proteins become abnormally phosphorylated.

Pick’s disease This used to be a term used for the clinical syndrome of FTD. However it is now used to mean a specific subtype of tau pathology.

Pluripotency The ability of a cell to turn into different types of cell.

Presymptomatic genetic testing The testing of individuals who are at risk of developing a disorder because they are from a family with a genetic disease.

Primary progressive aphasia or PPA The name for the group of disorders which present with progressive impairment of language skills. The main subtypes are semantic dementia and progressive nonfluent aphasia. In recent criteria these are called the semantic variant and nonfluent or agrammatic variant. A third subtype called logopenic aphasia or the logopenic variant is usually an atypical form of Alzheimer’s disease.

Progranulin This is a gene encoding the protein progranulin. Mutations in this gene cause FTD. Progranulin is a growth factor involved in many cell processes, including neuron growth.

Progressive nonfluent aphasia or PNFA This is one of the subtypes of PPA and presents with difficulty producing speech. The main symptoms are agrammatism and apraxia of speech. It is called the nonfluent variant of PPA in the new criteria.

Progressive supranuclear palsy or PSP This is the name for both a clinical syndrome and a type of pathology. The PSP clinical syndrome is a parkinsonian disorder with axial rigidity, falling backwards and a supranuclear gaze palsy. There can be overlap with bvFTD and PNFA. Pathologically, PSP is a subtype of tau pathology. It is almost always associated with the PSP clinical syndrome but may also more rarely present with other clinical syndromes such as CBS.

Prosopagnosia Difficulty recognizing faces.

Rigidity Stiffness, commonly in the limbs.

RNA Ribonucleic acid or RNA has a number of roles in our cells including forming an intermediate step between the DNA code in a gene and the protein that will be produced by the cell.

Salience network or SN A network of brain regions which share many connections and functions. The SN includes brain regions in the frontal, insular and subcortical regions of the brain. The SN appears highly specific to FTD as it affects brain regions which are commonly affected in FTD.

Selective serotonin uptake inhibitors or SSRIs A group of drugs that increase serotonin levels and are commonly used as antidepressants. There is some evidence for their use in FTD. They include fluoxetine, citalopram, paroxetine and sertraline.

Semantic dementia or SD This is a disorder of semantic knowledge, in other words our understanding of concepts and facts. The first symptoms are usually language problems such as difficulty finding the right word, or losing the meaning of words – people may ask what a previously known word means, for example “What is a tornado?”. It is called the semantic variant of PPA in the new criteria.

Sporadic A sporadic disease is one in which the disease occurs in an individual by chance, in other words it is not caused by a genetic abnormality.

Stem cell These are the master cells of the body and possess the property of pluripotency, or most potential.  This mean that stem cells have the potential to become any of the cell types of the body, including brain cells such as neurons or glia.

Supranuclear gaze palsy This is where people develop problems with movements of the eyes, commonly looking up and down. This is the one of the main features of PSP.

Synapse The site of connection between two neurons in the brain.

Transactive response DNA binding protein or TARDP This is the gene that codes for the TDP-43 protein.

Tau This is a microtubule-associated protein.  This means it binds to and stabilizes microtubules, allowing them to form in the correct place at the correct time.  In some cases of FTD, abnormal collections of tau form in the brain. The subtypes of tau pathology include PSP, CBD, Pick’s disease and the pathology seen with mutations in the MAPT gene.

TDP-43 TDP-43 is a DNA-binding protein, which is responsible for ensuring certain genes function in the correct way.  Collections of abnormal TDP-43 are seen in the brain in some people with FTD. There are four subtypes of TDP-43 pathology called A, B, C and D.

TMEM106B This is a gene that has been found in a GWAS study to be a risk factor for FTD.

VCP This is a gene coding for the valosin-containing protein.  Mutations in VCP are a rare cause of FTD, and can also cause ALS. Some patients with FTD due to VCP mutations also have two other diseases called inclusion body myositis and Paget’s disease of bone – together this group of disorders are called IBMPFD.